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)

A partially purified glycoprotein fraction (the G-200 II fraction) obtained from sera of CD-1 mice sensitized with Corynebacterium parvum and treated with endotoxin was designated as tumor necrosis factor (TNF). Human melanoma cells exposed to this factor in vitro had decreased tumorigenicity when injected into nude mice. Human melanoma, embryonal adenocarcinoma of the testis and colon carcinoma heterotransplanted in nude mice exhibited regressions in size following intraperitoneal injections of TNF. The responses were related to dose and duration of exposure.
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PMID:Effects of murine tumor necrosis factor on heterotransplanted human tumors. 43 45

Expression of the endothelial adhesion molecule VCAM-1 was studied in human malignant melanoma lines by flow cytometry. Clones 2/4 and 2/14 (derived from the same lesion) had appreciable levels of VCAM-1 expression, whereas clone 2/21 and the lines A2058, Mel24, and A375 were negative. Clone 2/14 was selected for further analysis. Exposure to tumor necrosis factor (TNF) markedly augmented VCAM-1 on melanoma cells. Surface VCAM-1 was associated with expression of specific transcripts that were augmented by TNF. Analysis by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that TNF-stimulated melanoma cells expressed both 7 and 6 immunoglobulin domain transcripts with predominance of the longer species. Tumor necrosis factor--stimulated melanoma cells bound more VLA-4-expressing cells (melanoma and monocytes) than resting tumor cells and anti-VCAM-1 monoclonal antibodies significantly inhibited binding, thus suggesting that surface VCAM-1 on melanoma is functional. Analysis of melanoma tissue sections demonstrated that VCAM-1 is not a marker of transformation of melanocytes because it can be detected in benign nevi. Although, unlike ICAM-1, VCAM-1 is not correlated with tumor progression, its expression in a fraction of primary melanomas indicates that it may play a role in regulating host immune response and homotypic interactions in some malignant melanomas.
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PMID:Regulated expression of vascular cell adhesion molecule-1 in human malignant melanoma. 128 17

A total of 22 patients with metastatic renal cell carcinoma or malignant melanoma were treated in a phase II study to assess the safety and efficacy of combination therapy of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha). 3 x 10(6) U/m2/day recombinant human (rh)IL-2 was given in repetitive cycles by continuous 24-h infusion from day 1 to day 4; 6 x 10(6) U/m2/day rhIFN-alpha was given subcutaneously on days 1 and 4. There was one complete remission and two partial remissions in the renal cell carcinoma group and two partial remissions in the malignant melanoma group, giving an overall response rate of 24% in 21 evaluable patients with a median response duration of 5+ months. Toxicity was moderate, with hypotension, fever, chills, nausea, neurotoxicity, and dermatitis as prominent side effects. Measurement of circulating cytokine levels showed increased serum tumor necrosis factor-alpha (TNF), interferon-tau, and soluble interleukin-2 receptor levels during each cycle with a tendency to higher concentrations of TNF in responders as compared to nonresponders. With regard to therapeutic efficacy and tolerance, our approach might represent an alternative to the high-dose protocols and the labor- and cost-intensive strategies of adoptive immunotherapy.
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PMID:Combination of interleukin-2 and interferon-alpha in renal cell carcinoma and malignant melanoma: a phase II clinical trial. 130 89

The in vitro effect of lithium on lymphokine-activated killer cell (LAK) activity and its in vivo antitumor growth were observed. LAK activity was enhanced when LiCl was added during LAK cell induction, and this enhancement was observed both in human peripheral blood mononuclear cell and in mouse splenocytes used as LAK precursors. Cholera toxin, which can increase intracellular levels of cAMP, decreased LAK cell activity. However, lithium partially reversed this inhibitory effect, indicating that lithium increased LAK cell activity by decreasing cAMP levels. D-Sphingosine, an inhibitor of protein kinase C, and EGTA, a calcium chelator, both inhibited the LAK cell activity. However, their inhibitory effects could not be reversed by lithium because lithium was added in the culture in combination with one of these inhibitors during LAK cell induction. By using slot blot analysis, the effect of lithium on the expression of tumor necrosis factor-alpha mRNA of LAK cells was analyzed. Lithium increased the level of tumor necrosis factor-alpha mRNA when both lithium and interleukin 2 were added to induce LAK cells. The in vivo antitumor effect of lithium has also been studied. Using a mouse melanoma experimental model, the effect of lithium on tumor growth was also observed. Both lithium alone and interleukin 2/LAK had an antitumor effect, whereas the treatment of interleukin 2/LAK in combination with lithium had the strongest inhibitory effect on tumor growth, since this treatment resulted in reduction of tumor size and prolongation of survival in tumor-bearing mice. Therefore, it is hopeful that lithium can be used as a new immunomodulator for cancer immunotherapy and immune diseases.
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PMID:Study of the effect of lithium on lymphokine-activated killer cell activity and its antitumor growth. 133 71

We have studied the cytokine regulation of cell surface and soluble intercellular adhesion molecule 1 (ICAM-1) expression on the human melanoma cell line A375M. Unstimulated cells express ICAM-1 on their cell surface but do not secrete significant levels of soluble ICAM-1. Interleukin 1, interleukin 6, tumor necrosis factor, and gamma-interferon all increased cell surface expression of ICAM-1. Tumor necrosis factor, interleukin 1, and gamma-interferon also caused the release of soluble ICAM-1. The serum of melanoma patients has been reported to contain elevated levels of soluble ICAM-1; however, the source of this ICAM-1 is unclear. The serum from nude mice bearing s.c. human melanoma tumors was found to contain soluble human ICAM-1. ICAM-1 levels showed a positive correlation with tumor weight. The release of ICAM-1 from melanoma tumors, in response to host-derived cytokines, may have relevance to immune recognition of the tumor.
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PMID:Soluble intercellular adhesion molecule 1 is released by human melanoma cells and is associated with tumor growth in nude mice. 134 68

Intercellular adhesion molecule-1 (ICAM-1, CD54), a molecule bound to the cell surface membrane, mediates various cell-cell interactions in inflammation and immunosurveillance. By means of a new specific enzyme-linked immunosorbent assay (ELISA) for soluble ICAM-1, free circulating ICAM-1 was measured in serum from five healthy volunteers, 10 melanoma patients at different stages of their disease, and eight patients receiving high-dose interleukin-2 (IL-2) for metastatic melanoma. No correlation between the concentration of circulating ICAM-1 and the tumor burden could be detected. In melanoma patients receiving high-dose IL-2, we observed an increase of circulating ICAM-1 of up to 200%, compared to the concentration prior to therapy, ranging between 4 and 13 ng/ml. The increase in circulating ICAM-1 was associated with the induction of tumor necrosis factor-alpha and interferon-gamma.
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PMID:Circulating intercellular adhesion molecule-1 in melanoma patients: induction by interleukin-2 therapy. 135 85

Five clones derived from the same human malignant melanoma lesion were studied for their susceptibility to killing by human monocytes activated by exposure to interferon (IFN)-gamma and lipopolysaccharide. Melanoma clones were heterogeneous in their susceptibility to human monocyte cytotoxicity, with one clone (2/21) exhibiting extremely low levels of lysis. The different levels of susceptibility to monocyte cytotoxicity were not accounted for by susceptibility or resistance to monokines [tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6] because: (a) these effector molecules had little (TNF) or no (IL-1 and IL-6) cytolytic activity under these conditions; and (b) anti-TNF antibodies had marginal effects on cytotoxicity. Monocytes bound less to resistant than to susceptible melanoma cells. Monocyte-resistant 2/21 melanoma cells expressed substantially lower levels of ICAM-1 and VLA-4 than susceptible cells. Anti-CD18 and, to a lesser extent, anti-ICAM-1 mAb inhibited binding and cytotoxicity of human monocytes on malignant melanoma whereas anti-VLA-4 had no inhibitory action. Transfection of the ICAM-1 gene under the control of a constitutive promotor resulted in high levels of expression of ICAM-1 in 2/21 melanoma cells and, concomitantly, in augmented susceptibility to activated monocyte cytotoxicity. The augmented killing of ICAM-1 transfected 2/21 cells was inhibited by anti-ICAM-1 mAb. These results demonstrate that the CD18-ICAM-1 adhesion pathway can play an important role in the expression of human monocyte cytotoxicity on melanoma target cells and that heterogeneity in expression of ICAM-1 can underlie differences in susceptibility to tumoricidal activity.
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PMID:Heterogeneous susceptibility of human melanoma clones to monocyte cytotoxicity: role of ICAM-1 defined by antibody blocking and gene transfer. 135 29

We have examined the mechanisms by which tumor cells bind to endothelial cells utilizing cultured melanoma cells and microvascular endothelial cells derived from human dermis (HDMEC). The ability of biologic response modifiers (BRM) to modulate the adhesion of melanoma cells to HDMEC was defined and those results were compared with results from human umbilical vein endothelial cells (HUVEC). SK-MEL-2, WM266-4, and Hs 294T melanoma cells all bound to HDMEC and HUVEC monolayers and adherence of melanoma cells was enhanced in a dose- and time-dependent manner by the treatment of HDMEC with interleukin 1 (IL-1) alpha or tumor necrosis factor (TNF) alpha. Similar increases in binding to HDMEC or HUVEC were induced after BRM stimulation, although baseline melanoma cell binding to HUVEC tended to be slightly higher than to HDMEC. In contrast, whereas phorbol 12-myristate 13-acetate (PMA) augmented melanoma cell adherence to HDMEC, PMA failed to increase adherence to HUVEC. The alterations in melanoma cell binding were induced only after pretreatment of endothelial and not melanoma cells with PMA. Studies of the expression of cell adhesion molecules (CAM) on HDMEC and HUVEC using enzyme-linked immunosorbent assay showed that vascular cell adhesion molecule 1 (VCAM-1) is not induced by PMA on HDMEC and intercellular adhesion molecule 1 (ICAM-1) is downregulated on HDMEC by PMA treatment. Endothelial leukocyte adhesion molecule 1 (ELAM-1) is induced by PMA, IL-1 alpha, or TNFalpha, but its expression does not correlate with increased melanoma cell binding MoAb recognizing VCAM-1-inhibited TNFalpha-induced increases in melanoma cell binding to HUVEC. However, anti-VCAM-1 antibody failed to clock melanoma cell binding to PMA or IL-1 alpha-stimulated HDMEC and only partially inhibited melanoma cell binding to TNF alpha-stimulated HDMEC. This study demonstrates that PMA and IL-1 alpha-induced increases in melanoma cell adherence to HDMEC are not mediated via known CAM, including ICAM-1, VCAM-1, or ELAM-1, and may be affected through microvessel-specific novel proteins not previously described on endothelial cells.
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PMID:VCAM-1-, ELAM-1-, and ICAM-1-independent adhesion of melanoma cells to cultured human dermal microvascular endothelial cells. 137 Feb 33

The intrathecal immune response in neoplastic meningitis (NM) was studied by quantitation of immune parameters such as immunoglobulin G (IgG); IgM; interleukins (IL) 1, 2, 4, and 6; soluble IL-2 receptors (sIL-2R); interferon gamma (IFNy); tumor necrosis factor-alpha (TNF alpha); and three tumor markers, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and fibronectin (FN), in 47 paired cerebrospinal fluid (CSF) and serum samples from patients with NM from different carcinomas, malignant melanoma, and lymphoma. Elevated IgG and IgM indices, CSF oligoclonal Ig bands, and CSF IL-6 indicated an intrathecal immune activation in most patients with NM. Results for IL-1, IL-2, and IL-4 were always negative. sIL-2R and IFNy were detected occasionally but not associated with specific malignant neoplasms. CSF TNF alpha was detected only in NM from cases of malignant melanoma. None of the immune parameters proved useful for the differentiation of NM from autoimmune or inflammatory conditions. Immune parameters were not correlated with tumor markers CEA, AFP, or FN. Results for AFP were positive only in a case of glioblastoma. CEA was a useful and specific diagnostic parameter in carcinomatous NM. CSF FN levels frequently were elevated but are not specific for NM.
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PMID:Tumor cell dissemination triggers an intrathecal immune response in neoplastic meningitis. 137 13

The effect of the administration of recombinant interferon-gamma (rIFN-gamma) and a synthetic lipid A subunit analog (GLA-60) on angiogenesis induced by B16-BL6 melanoma was examined in syngeneic C57BL/6 mice. Intravenous administration of rIFN-gamma followed by GLA-60 (referred to as rIFN-gamma/GLA-60) induced endogenous production of tumor necrosis factor (TNF). This treatment on day 3 after tumor inoculation caused a marked decrease in the number of vessels oriented towards the tumor mass (angiogenic response) and tumor size over a period of 9 days. In contrast, neither rIFN-gamma nor GLA-60 alone, nor GLA-60/rIFN-gamma (reverse sequence of administration), which is unable to induce the production of TNF in the serum, had any effect. Sera induced by the treatment with rIFN-gamma/GLA-60, and recombinant TNF, inhibited the in vitro growth of lung endothelial cells which is considered to be one of the essential events in tumor neovascularization. Multiple i.v. treatments with rIFN-gamma/GLA-60 on days 5, 8 and 11 after s.c. implantation of tumor significantly inhibited primary tumor growth by the amputation time (day 20) and lung metastasis of B16-BL6 cells on day 34, while other treatment modalities had no such effect. Our results indicate that inhibition of lung-tumor metastasis by rIFN-gamma/GLA-60 treatment may be partly due to the inhibition of tumor-associated angiogenesis.
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PMID:Inhibition of tumor-induced angiogenesis by the administration of recombinant interferon-gamma followed by a synthetic lipid-A subunit analogue (GLA-60). 137 2


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