Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1522102 (Melanoma)
 7,698 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gangliosides expressed by normal melanocytes are predominantly GM3 (greater than 90%) and GD3 (less than 5%). Malignant melanoma can express several other types of gangliosides in significant quantities, including GM2 and GD2. Melanoma patients can develop an immune response against some of these ganglioside antigens on autologous melanoma cells. The four major gangliosides expressed by human melanoma cells (GM3, GD3, GM2, and GD2) were examined for their immunomodulatory effect on lymph node lymphocytes from melanoma patients. Gangliosides were added exogenously to lymphocytes grown in the presence of IL-2. Preferential interactions of specific melanoma gangliosides on IL-2 stimulation were found. While GM2 and GD2 enhanced the lymphocyte response to IL-2, GM3 and GD3 significantly inhibited this response. GM2 and GD2 differ from GM3 and GD3 by the presence of a terminal N-acetylgalactosamine. Since different gangliosides can up-regulate and down-regulate lymphocyte responses to IL-2, the ganglioside phenotype of melanoma cells may play a major role in determining whether an individual tumor causes immune stimulation or suppression.
 ...
PMID:Gangliosides from human melanoma immunomodulate response of T cells to interleukin-2. 312 73

We conducted a pilot study using liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) preoperatively in patients with stage III or IV resectable melanoma who were at high risk for recurrence. Patients received L-MTP-PE for 1 month before surgery and then 5 months postoperatively. Several immune parameters were monitored during preoperative therapy to search for correlations with clinical (tumor) response. The 18 patients were classified into three groups according to their responses and disease-free intervals: no evidence of disease (NED) at week 24 of therapy, relapse during therapy and progressive disease on therapy noted at the time of surgery. Six of nine patients in the NED group demonstrated increased monocyte tumoricidal activity (MTA) during week 1 of therapy. MTA increased in three of the six patients in the relapse group. MTA did not increase in the three patients who had progressive disease on therapy. Plasma neopterin levels were elevated by 72 h following the first L-MTP-PE dose in all 18 patients. Circulating levels of tumor necrosis factor were elevated in 15 of 16 patients tested, and IL-6 levels were elevated in all 18 patients. Melanoma cells from all three patients with progressive disease at the time of surgery proliferated well in vitro, whereas tumor cells from 10 of the 15 patients in the other two groups did not proliferate. There were no discernible differences among the three groups in the magnitude of IL-2-induced proliferation of tumor infiltrating lymphocytes. However, IL-2-activated TILs from the NED group exhibited cytotoxicity against autologous tumor cells in vitro. In summary, whereas L-MTP-PE stimulated several immunologic responses in all patients, the only two parameters that correlated with clinical status were MTA and the tumor proliferation assay. These two biologic assays could serve to distinguish potential responders from nonresponders early in the course of treatment.
 ...
PMID:Cytokine production and immune cell activation in melanoma patients treated with liposomal muramyl tripeptide (CGP 19835A lipid). 780 72

The murine melanoma cell line BL-6-beta m, which is a stable cell line transfected with a gene coding a unique actin subspecies called beta m to the BL-6 cell line, has low metastatic potentials as compared with those of the parent cell line. BL-6-beta m melanomas were found to be sensitive to in vivo local injection of IL-2, while BL-6 melanomas showed almost no response. Ganglioside analysis of BL-6 and BL-6-beta melanomas revealed that the main ganglioside of both melanomas was GM3, which suggested that different sensitivities between BL-6 and BL-6-beta m melanomas to the injection of IL-2 did not relate to the different compositions of main gangliosides. However, minor components of the gangliosides such as GM2 and GM1 emerged only in BL-6-beta m melanomas after treatment with IL-2. Local injection of IL-2 caused considerable infiltration of anti-asialo GM1-positive cells into the nests as well as the interstitials of BL-6-beta m melanomas. In contrast, in the BL-6 melanomas treated with IL-2, infiltration of the anti-asialo GM1-positive cells was hardly seen, although anti-Thy1,2 and anti-macrophage-positive cells were found to more or less the same extent as observed in BL-6-beta m melanomas. These results suggest that the murine metastatic variant melanoma cell lines BL-6 and BL-6-beta m have different properties in terms of sensitivity to in vivo IL-2 treatment, and a slight enhancement of the ganglioside components GM2 and GM1 expression only in BL-6-beta m after IL-2 treatment may play a role in the IL-2-mediated attraction of immune cells or may explain the different sensitivities of the two lines to treatment with IL-2.
Melanoma Res 1994 Oct
PMID:Different sensitivities of the murine melanomas BL-6 and BL-6-beta m to local injections of interleukin-2 (IL-2). Analysis of gangliosides after the treatment. 785 13

MHC-restricted recognition of melanoma cells by cytotoxic T lymphocytes is an important mechanism in vitro. Several HLA alleles can function as restriction elements for melanoma cell recognition. In this study we investigated whether there is a correlation between responsiveness of patients with metastatic melanoma (MM) to immunotherapy and the HLA type of the patient. Seventy-two patients received immunotherapy with IFN-alpha and IL-2 according to two different schedules with an overall response rate of 24%. In 54 patients, including 16 responders and 16 patients with stable disease, in whom peripheral blood lymphocytes were available, we determined HLA haplotypes. As a control group we prospectively determined HLA types in 67 melanoma patients of all stages who underwent surgery or received chemotherapy and of 126 healthy donors from our blood bank. Two HLA alleles that have been shown to function as restriction elements in vitro were observed more frequently in responding patients, namely Cw7 (p = 0.014) and A1 (p = 0.19). No association was found for A2 and B44. These observations provide evidence that the responsiveness of MM to immunotherapy with IL-2 is associated with certain HLA types, suggesting an important role of HLA-restricted T lymphocytes for IL-2-induced tumour regression.
Melanoma Res 1994 Jun
PMID:HLA class I alleles and responsiveness of melanoma to immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). 791 65

Melanoma patients with very advanced disease have usually not been included in chemo-immunotherapy trials. We report on 22 melanoma patients, including 5 with reduced performance status (Karnofsky PS < 70), 8 with metastatic ocular melanoma, 6 with brain metastases, and 4 who had pretreatment with interleukin-2. These were treated with a combination regimen of dacarbazine (250 mg/m2, days 1-3), cisplatin (30 mg/m2, days 1-3), interferon-alpha 2a (IFN-alpha, 10 Mio IU/m2 s.c., days 1-5) and IL-2 (i.v., 18 Mio IU/m2 for 6, 12, 24 h, followed by 13.5 Mio IU/m2 in 72 h). In the case of brain metastases radiotherapy was added. No grade IV toxicity occurred and no dose reductions were necessary. 21 patients were evaluable for response. 6 (29%) had disease progression, 5 (24%) had partial response and 10 (48%), had stable disease. Sites of response included skin, lymph nodes, muscle, lung, pleura, liver, pancreas, adrenal gland and brain. The described treatment schedule is safe and active even in patients with metastatic melanoma and poor prognosis.
 ...
PMID:A phase II study of dacarbazine, cisplatin, interferon-alpha and high-dose interleukin-2 in 'poor-risk' metastatic melanoma. 891 Nov 13

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

The incidence of Cutaneous Melanoma is 4-5% of all the tumors of the skin. This incidence increases several folds in the last years. Metastases of Melanoma involve lungs, skin, soft tissue, liver, bone, brain, but in 20-30% of the patients involve gastrointestinal (GI) tract. In 60-70% of the cases GI metastases involve small bowel, in 15-20% stomach, in 10-20% large bowel, in 5% esophagus. In 8% of the patients the primary cutaneous melanoma is not known. The prognosis of the patients with metastatic melanoma is poor with an average survival of 5 months. One patient male, 51 years old, underwent surgery for metastases from melanoma in the lymph nodes of the right axilla and in the gastrointestinal tract (ileum). An ileo-ileo anastomosis and a lymphoadenectomy of the nodes of the right axilla were performed. After a first chemotherapy with DTIC (800 mg/m2) + a-IFN(3MU three times every week) and another with CDDP (30 mg/m2 day 1-3), DTIC (250 mg/m2 day 1-3) and VDS (2.5 mg/m2 day 1) with no response, the patient was treated with chemo-immunotherapy sec. Bernengo, slightly modified: CDDP 75 mg/m2; IL-2 18 MU (9MU b.d.) day 3-6 and 17-21; a-IFN 5MU three times every week. This therapy had a partial response of short-course (three months) and the patient died 15 months after surgery. The authors hope that immunotherapy and genetic therapy improve the survival of the patients with metastatic melanoma in the next years.
 ...
PMID:[Ileal and axillary metastasis of primary unknown site melanoma. Clinical case]. 945 53

MELP is an interleukin (IL)-2 receptor (IL-2R; alpha+ beta+ gamma-) melanoma cell line that was derived, before the beginning of the immunotherapy, from a patient whose metastasis increased in size during treatment with IL-2/interferon-alpha. In these cells, continuous culture in the presence IL-2 (1000 UI/ml) causes the selection of a cell sub-line (termed MILG) expressing the gamma-chain which is tumorigenic in nude mice. Here, we further analysed the characteristics of MELP and MILG cells as well as clones selected at limiting dilution in the presence of high concentrations of IL-2 or IL-15, or those selected after transfection for the expression of a human IL-2 transgene (MELP-CL1). MELP cells, but not six other melanomas cell lines, shed two soluble immunosuppressive molecules, CD25 and intercellular adhesion molecule-1, whose levels also strongly increase in vivo during immunotherapy. In vitro MELP cells express transcripts for IL-6, transforming growth factor, basic fibroblast growth factor and vascular-endothelial growth factor. Cloning at limiting dilution was obtained in culture fed with IL-2 or IL-15. All these clones, as MILG cells, express the transcript for the IL-2R gamma chain. This could favour improved interactions with cytokines using this chain. By contrast, MELP-CL1 cells, which secrete low amounts of biologically active IL-2 (200 UI/10(6) cells) exhibit a phenotype and growth characteristics similar to those of the parental MELP cells. Indeed, a crosslinking experiment with 125I-IL-2, has showed that MELP and MELP-CL1 cells display a scant IL-2 binding ability that is strongly increased in MELP cells fed for 1 week with 1000 UI/ml IL-2. These cells, as well as MILG cells express a betagamma-complex which can also bind IL-15. IL-2 induces a rapid tyrosine phoshorylation in MILG cells, which is followed by a prolonged induction of c-fos and c-jun genes. By contrast, in MELP cells IL-2 only causes a delayed induction of c-myc gene. All MELP derivatives, but not MILG cells, express the transcripts for IL-15, which is not secreted but is present as an intracellular protein. All MELP cells express the transcript for the IL-15R alpha chain. MELP-CL1 cells are not tumorigenic in nude mice, whereas MILG cells form rapidly growing tumours in 75% of the mice. Coinjection at the same site of MILG and MELP-CL1 cells causes the rapid regression of MILG tumours in 80% of the mice, whereas their bilateral injection causes the rapid development of MILG tumours in 100% of the nude mice. Finally, treatment in nude mice of MILG cells with low amounts of IL-2 (1000 UI per mouse) and IL-15 (50 ng per mouse) induces the development of much more aggressive tumours.The expression of functional IL-2Rs in a subset of human melanomas could be responsible for tumour progression.
Melanoma Res 1997 Aug
PMID:Role of interleukin (IL)-2 and IL-15 in the tumour progression of a melanoma cell line MELP, derived from an IL-2 progressor patient. 957 12

The annual incidence of malignant melanoma is estimated at 10-12 per 100,000 inhabitants in countries of central Europe and the United States, and alarmingly there has been a dramatic upward trend in that estimate. The B16 murine melanoma is a rapidly growing metastatic tumor of spontaneous origin, as are human malignant melanomas. Melanoma cells produce specific antigens which are uniquely different from normal cellular antigens, and the expression of such antigens is the cornerstone for preparation of anti-melanoma vaccines. One major problem in evaluating the effectiveness of vaccination and other biologic therapies is the variability of experimental tumor models. A new metastatic model of experimental melanoma which was developed in our laboratory imitates the major clinical stages of malignant metastatic melanoma: stage I, primary (local) tumor growth and bone marrow invasion; stage II, regional lymph node involvement; and stage III, metastasis to distant organs, such as the lungs. This model has been used successfully for screening vaccines constructed in our laboratory. Immunization with formalinized vaccines (of extracellular antigens, intact melanoma cells, or B700 antigen) or irradiated vaccines (of intact melanoma cells) partially inhibit primary melanoma tumor growth, reduce metastasis to regional lymph nodes and lungs, and significantly increase mean survival time. These anti-tumor effects were improved when polyvalent and monovalent vaccines were combined with IL-2 therapy. We also compared the immunogenic activity of vaccines made from B16 melanoma cells transfected with genes encoding murine IL-2 or GM-CSF, and effects on tumor bearing mice were compared with or without therapy using the corresponding lymphokines. In sum, comparison of antibody production, growth of primary melanoma tumors, number of surviving mice, mean survival time, and percent of mice with lung metastases, showed that the best course of immunotherapy involves vaccination of mice with irradiated B16 melanoma cells transfected to secrete GM-CSF, coupled with GM-CSF therapy.
 ...
PMID:A new mouse model of experimental melanoma for vaccine and lymphokine therapy. 966 34

Melanoma cells in culture express a variety of growth factors and cytokines and some of their autocrine and paracrine roles have been investigated. However, less information is available on the potential dynamic changes in expression of these molecules on cells during melanoma development and progression in situ. Using immunohistochemistry, we tested 40 nevi and primary and metastatic melanoma lesions for the expression of 10 growth factors and cytokines and the respective receptors representing 10 cell surface molecules. Nevi and thin (< 1 mm) primary melanomas showed little expression of ligands except weak reactivity of tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8) and reactivity of TGF-betaR and c-kit. Marked up-regulation of growth factors, cytokines and receptor expression was observed in thick (> 1 mm) primary melanomas, which were stained with polyclonal or monoclonal antibodies (MAbs) for IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, TGF-beta, granulocyte-macrophage colony-stimulating factor (GMCSF) and stem cell factor (SCF), but not IL-2. Metastases showed similar expression patterns except that SCF was absent. Co-expression of ligand and receptor was observed for TGF-beta, GM-CSF and IL-6, suggesting an autocrine role for these ligands. TNF-alpha appears to be a marker of benign lesions; IL-6 and IL-8 expression is associated with biologically early malignancy; TGF-beta, GM-CSF and IL-1alpha are highly expressed in biologically late lesions; and TNF-beta is an apparent marker of metastatic dissemination. Our results indicate that melanoma cells utilize cascades of growth factors and cytokines for their progression.
 ...
PMID:Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions. 1009 49


1 2 3 4 5 Next >>