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

As a preliminary to transducing human melanoma cells with lymphokine genes, we sought for constitutive gene expression and production of eight interleukins, tumour necrosis factors and granulocyte-colony stimulating factor in 19 human melanoma cell lines. Conversion of RNA into cDNA by reverse transcriptase and polymerase chain reaction (RT-PCR) were employed to evaluate gene expression while enzyme-linked immunosorbent assays (ELISA) or biological assays were used to assess the presence of proteins. No expression of interleukins (IL) 3, 4, and 5 or interferon-gamma RNA was found, while the other cytokines were variably expressed in melanoma lines, with IL-1 alpha, IL-1 beta, IL-6, IL-8, being detectable in most of the lines. At protein level, 10 melanoma cells were tested with ELISA and all were found to produce IL-8, five produced IL-6, two tumour necrosis factor (TNF)-alpha, one IL-1 alpha and two TNF beta. The levels of TNF beta were at the limit of test sensitivity. The amount of various cytokines released by the different lines varied widely. Biological assay with the D10-G4 clone confirmed the presence of IL-1 alpha in the supernatant of melanoma (ME) 10221 and revealed an IL-1 activity in the supernatant of Me 4024/1. The proliferating activity of melanoma supernatants on D10-G4 was inhibited by treatment with polyclonal antibodies against IL-1 alpha but not with antibodies against IL-1 beta. TNF biological activity was tested against the TNF-susceptible fibrosarcoma WEHI 164 clone 13.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res 1992 Sep
PMID:Expression of cytokine genes, including IL-6, in human malignant melanoma cell lines. 145 Jun 72

The human melanoma-associated antigen identified by the monoclonal antibody (mAb) Me14-D12 is a cell surface protein whose expression is induced by interferon-gamma (IFN-gamma). We have recently reported the molecular cloning of a genomic probe specific for the gene and mRNA of this protein. By screening with the genomic probe, we have now isolated a full length 3.0 kb cDNA from a Raji cell line-derived lambda-gt10 library. Sequence analysis of this cDNA showed a 99.8% homology with the intercellular adhesion molecule-1 (ICAM-1). Mouse Ltk- cells stably transfected with the human cDNA clone were found to express the ICAM-1 antigenic determinants detected by mAb Me14-D12 and a reference anti-ICAM-1 mAb, as judged by surface immunofluorescence. Immunoprecipitation of surface-iodinated proteins with mAb Me14-D12 revealed the presence of a 90 kD molecule with identical mobility to ICAM-1. In addition, mAb Me14-D12 could inhibit the phorbolester-stimulated aggregation of U937 cells. The findings show that the human melanoma-associated Me14-D12 antigen is the adhesion molecule ICAM-1.
Melanoma Res
PMID:Cloning of an interferon-gamma regulated human melanoma-associated antigen: identity to the intercellular adhesion molecule ICAM-1. 168 67

Melanoma cell lines treated with or without interferon-gamma were tested for the presence of DR alpha mRNA and protein. The six lines examined fell into three general categories: two that expressed high levels of DR alpha mRNA and protein before and after interferon-gamma treatment, one that expressed very low levels before treatment with interferon-gamma, but was induced to express high levels after interferon-gamma treatment, and three that expressed very low levels before treatment, and were only slightly inducible after treatment with interferon-gamma. The presence of DR-alpha protein on the melanoma cell surface was always positively correlated with the presence of DR alpha mRNA in the cells. Furthermore, in the cell line that was interferon-gamma-inducible, the time at which DR alpha mRNA and protein appeared and the doses of interferon-gamma needed to induce this appearance were directly correlated. Methylation patterns of the DR alpha gene in these cell lines were also studied in order to determine whether the degree of DR alpha gene methylation among the lines correlated with expression of the gene. Digestion of DNA with the restriction enzyme MspI, which recognizes the sequence 5'CCGG3' and 5'CmCGG3', led to the appearance of a 3.1 kb band from all lines tested. Hpa II digestion, which recognizes 5'CCGG3', but not 5'CmCGG3', led to the appearance of 3.1, 4.4, and 6.7 kb bands in all lines tested except for DUMEL 8, which showed only the 3.1 kb band. Interestingly, DUMEL 8 expressed very low levels of DR alpha mRNA and protein before and after interferon-gamma treatment. We conclude that interferon-gamma has a regulatory effect on DR alpha genes of various melanoma cell lines to varying degrees. This may reflect an effect of interferon-gamma on certain subpopulations of melanocytes in vivo. Our data also indicate that partial methylation of the DR alpha gene does not inhibit its expression. Furthermore, interferon-gamma does not appear to induce expression of the DR gene by altering methylation patterns within the region recognized by our probe.
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PMID:Differential expression of the HLA-DR genes in various melanoma cell lines treated with interferon-gamma: methylation of the HLA-DR alpha gene in these lines is not correlated with its expression. 310 41

LM mouse fibroblasts (H-2k) were modified for the expression of (antibody-defined) melanoma-associated antigens (MAA) and the secretion of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) (RLBA-IL-2/IFN-gamma cells). The cell construct was tested for its immunogenic properties in C57BL/6 mice (H-2b) with B16 melanoma. The results indicated that the survival of mice injected with a mixture of B16 cells and the modified, double cytokine-secreting fibroblasts was significantly longer than that of mice injected with B16 cells and LM cells modified for the expression of MAA and the secretion of IL-2 or IFN-gamma alone (RLBA-IL-2 or RLBA-IFN-gamma cells). Both natural killer/lymphokine-activated killer (NK/LAK) cells and Lyt-2.2 + CTLs with anti-melanoma cytotoxic activities were predominant in mice immunized with the double cytokine-secreting cells. B16 melanoma cells persisted in mice treated with RLBA-IL-2 cells (B16-R3). The B16-R3 cells were resistant to anti-melanoma effector cells from mice immunized with RLBA-IL-2 cells. The recurrent melanoma cells were deficient in the expression of MHC class I determinants. Class I expression by B16-R3 cells was increased if they were incubated in medium conditioned by the growth of IFN-gamma-secreting RLBA-IL-2/IFN-gamma or RLBA-IFN-gamma cells. After incubation, the sensitivity of B16-R3 melanoma cells to immune-effector cells from mice immunized with RLBA-IL-2 cells was restored. The survival of mice bearing low MHC class I-expressing B16-R3 cells, treated RLBA-IL-2/IFN-gamma cells, was determined. The treated animals survived significantly longer than mice with B16-R3 melanoma treated with RLBA-IL-2 cells. Similar results were obtained for mice with B16-R3 melanoma treated with RLBA-IFN-gamma cells. We postulate that immunization of mice with IL-2/IFN-gamma double cytokine-secreting cells stimulated multiple anti-melanoma effector mechanisms. Analogous to the enhanced therapeutic anti-tumour effects of combination chemotherapy, it was likely that treatment with a cellular immunogen engineered to stimulate more than one effector mechanism resulted in the elimination of larger numbers of tumour cells than treatment with an immunogen that stimulated a single effector mechanism alone.
Melanoma Res 1995 Aug
PMID:Immunization with interleukin-2/interferon-gamma double cytokine-secreting allogeneic fibroblasts prolongs the survival of mice with melanoma. 749 56

Adhesion molecules are likely to play a role in the process of tumour progression. We investigated the expression of integrins, ICAM-1, and CD44 and the influence of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and tumour necrosis factor-alpha (TNF-alpha) on expression of these molecules on four uveal melanoma cell lines. The in vitro integrin expression was quite variable. The alpha V and beta 1 subunits were expressed on all cell lines, and none of the cell lines showed any alpha 3, beta 2, or beta 4 expression. Other integrin subunits showed a more variable pattern. ICAM-1 and CD44 were strongly expressed on all cell lines. IFN-alpha, IFN-gamma, and TNF-alpha upregulated alpha 1, alpha 2, and alpha 3 expression, and did not alter alpha 4, alpha 5, alpha 6, beta 2, alpha v beta 3, and beta 4 expression. The effects on alpha V and alpha V beta 5 were variable. ICAM-1 was upregulated by IFN-gamma and TNF-alpha, but not by IFN-alpha. Cytokine treatment hardly changed CD44 expression. In one case a comparison was made between expression on cultured cells and on tissue sections of the tumour of origin. Differences in expression were observed for the integrin subunits alpha 2, alpha 3, and alpha 5. This study shows that integrins and ICAM-1 expression on uveal melanoma cells in vitro are susceptible to cytokine treatment, but that the effects on integrin expression are cytokine and cell line dependent. Furthermore, some differences in integrin expression between cells in vivo and in vitro exist.
Melanoma Res 1995 Aug
PMID:Cytokine-mediated modulation of integrin, ICAM-1 and CD44 expression on human uveal melanoma cells in vitro. 749 58

The combination of chemotherapy and immunotherapy seems to improve response rate in metastatic melanoma. We investigated the effects on toxicity and immunological effects of a single dose of dacarbacin (DTIC; 850 mg/m2) or cisplatin (CDDP; 100 mg/m2) added to subsequent immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-alpha/IL-2 alone were studied. Six received DTIC and IFN-alpha/IL-2, and six received CDDP and IFN-alpha/IL-2. DTIC did not add significant toxicity except for nausea. Significant thrombocytopenia was observed in two patients after CDDP. Although CDDP led to grade 3 nephrotoxicity in two patients, the IL-2-induced fluid retention was less severe than with IFN-alpha/IL-2 alone. Pharmacokinetics of IL-2 were not altered by DTIC, but higher IL-2 serum levels were found in patients with grade 3 nephrotoxicity after CDDP. The IL-2-related induction of secondary mediators (interferon-gamma, tumour necrosis factor-alpha, soluble CD25) was not impaired by chemotherapy and the induction of neopterin was significantly higher after addition of CDDP. One partial response was observed after addition of DTIC to IFN-alpha/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-alpha/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy.
Melanoma Res 1995 Aug
PMID:Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects. 749 66

The Surgery Branch of the National Cancer Institute has initiated several clinical trials involving the use of high-dose TNF in isolated limb perfusions. A phase III trial compares the three drug combination of TNF, interferon-gamma (IFN-gamma) and melphalan with a standard melphalan-alone perfusion in a prospective randomized trial. Another protocol escalates the dose of TNF in the perfusate to define the maximally tolerated dose that can be administered in this regional manner. A third protocol adds systemic high-dose interleukin-2 postoperatively to a TNF, IFN, and melphalan limb perfusion for patients with stage IV melanoma with the bulk of the disease in the extremity. This brief review highlights the rationale and study design of these TNF limb perfusion protocols.
Melanoma Res 1994 Mar
PMID:The use of tumour necrosis factor (TNF) in isolated perfusion: results and side effects. The NCI results. 803 92

We examined the role of cell adhesion molecules (CAM) by which tumor cells bind to the endothelial cells using human umbilical vein endothelial cells (HUVEC) and cultured melanoma cells. Endothelial cells from human umbilical veins were isolated and examined for CAM expression and its modulation by tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) or interferon-gamma (IFN-gamma). The expression of intercellular adhesion molecule 1 (ICAM-1) on HUVEC was increased by TNF-alpha, IL-1 and IFN-gamma when measured by ELISA or flow cytometric (FACS) analysis. IL-6 did not increase ICAM-1 expression on HUVEC. Two melanoma cell lines, Malme-3M and SK-Mel-28, showed increased expression of ICAM-1 after treatment with TNF-alpha, IL-1 and IFN-gamma in FACS analysis. IFN-gamma induced increased expression of HLA-DR only in SK-Mel-28 melanoma cells, not in Malme-3M melanoma cells. Neither HUVEC nor melanoma cells expressed lymphocyte function-associated antigen 1 (LFA-1) in either the basal (i.e., cytokine untreated) condition or the cytokine treated condition. Melanoma cells showed minimal increment in adhesion to TNF-alpha or IL-1 treated HUVEC than to cytokine untreated HUVEC. HUVEC and melanoma cells did not express LFA-1 and increased ICAM-1 expression by TNF-alpha, IL-1 and IFN-gamma treatment in FACS analysis did not coincide with minimal increase of melanoma cells adhesion to cytokine treated HUVEC. These results suggest that adhesion between melanoma cells and HUVEC is probably mediated by molecular interaction other than ICAM-1/LFA-1.
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PMID:Effect of cytokines on the expression of cell adhesion molecule and on the adhesion of melanoma cells to endothelial cells. 810 61

The aim of this study was to determine if human melanoma cells could be molecularly modified by particle-mediated gene transfer with a "gene gun", using genes for interferon-gamma (IFN-gamma), the B7-1 costimulatory molecule (CD80), and human leukocyte antigen (HLA)-A2, to augment expression of both HLA molecules and B7-1. Established and early passage melanoma cells transfected with human IFN-gamma complementary DNA (cDNA) produced IFN-gamma (50-5,000 pg/mL). The biological effect of this IFN-gamma transgene included an upregulation, or de novo appearance, of HLA expression. These melanoma cells had no detectable baseline surface expression of the B7-1 costimulatory molecule, but 8% to 31% of these cells became B7-1 positive with no selection procedure after gene transfer with human B7-1 cDNA. After combination gene transfer with cDNAs for both IFN-gamma and B7-1, 9% to 33% of these cells expressed both HLA-DR and B7-1. In combination gene transfer experiments with cDNAs for both HLA-A2 and B7-1, dual expression of HLA-A2 and B7-1 was achieved in 10% to 17% of the melanoma cells. Thus, the molecular modification of human melanoma cells to increase expression of both HLA and B7-1 can be achieved by particle-mediated gene delivery and presents a promising strategy to stimulate antimelanoma T-cell immunity. Key words: Melanoma; T cells; B7-1 costimulatory molecule (CD80); major histocompatibility complex.
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PMID:Dual expression of human leukocyte antigen molecules and the B7-1 costimulatory molecule (CD80) on human melanoma cells after particle-mediated gene transfer. 872 84

Interferon regulatory factor-1 (IRF-1) is a cell growth inhibitor, induced by cytokines, which transactivates downstream effector genes. The role of IRF-1 in the antiproliferative effect of interleukin-6 (IL-6) was investigated using the A375 human melanoma cell line. IL-6 is a stronger inhibitor of A375 proliferation compared with interferon-gamma (IFNgamma). However, in contrast to IFNgamma, IL-6 triggered lower IRF-1 DNA binding activity and induced barely detectable IRF-1-dependent transactivation activity. Furthermore, although IFNgamma induces only activation of signal transducer and activator of transcription (STAT) 1, IL-6 activates mainly STAT3. These data suggest that IRF-1 plays a minor role in the antiproliferative effect of IL-6, which uses alternative signalling events to induce growth inhibition in A375 melanoma cells.
Melanoma Res 1998 Feb
PMID:Interferon-gamma and interleukin-6 inhibit proliferation in human melanoma cells by different signalling pathways. 950 73


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