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)

Hyperthermia treatment has been shown to enhance the in vitro antiproliferative effects of IFN-alpha, IFN-beta, and IFN-gamma, with IFN-gamma being more strongly enhanced than IFN-alpha. The comparative effects of hyperthermia on the in vivo antitumor activities of IFN-alpha and IFN-gamma were evaluated in the murine system using both subcutaneous and intraperitoneal B16 melanoma tumor model systems. Heat-induced whole body hyperthermia, resulting in a 2 degree C rise in body temperature, was administered by incubating the mice for 8 hours in a dry incubator at 37.1 degrees C. Whole body hyperthermia was found to enhance the antitumor activity of IFN-alpha by approximately 1.0 fold and 1.2 fold for the subcutaneous and intraperitoneal tumor models, respectively. This represented an additive effect of hyperthermia and IFN-alpha. Hyperthermia was found to enhance the antitumor activity of IFN-gamma by approximately 2.9 fold and 2.2 fold for the subcutaneous and intraperitoneal tumor models, respectively. This represented a synergistic effect of hyperthermia and IFN-gamma. The results of this in vivo study confirm and extend the in vitro observation that hyperthermia more strongly enhances the antitumor action of IFN-gamma than IFN-alpha. These results may have clinical importance because they suggest that hyperthermia may be used in combination with IFN-gamma to provide a synergistically enhanced antitumor action.
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PMID:Effect of hyperthermia on the antitumor actions of interferons. 128 87

Expression of the Ly-6A/E gene by transformed cells was investigated in 14 cell cultures of C57BL/6 and BALB/c mouse origin derived from spontaneous or chemically-induced non-hematopoietic tumours and from cells transformed by SV40 virus. Histologic types included carcinomas, sarcomas and a melanoma. Thirteen out of 14 cell cultures expressed membrane Ly-6A/E antigens; only the B16-A melanoma was negative, but it expressed Ly-6A/E after incubation with IFN-gamma. The effect of in vitro permanence was studied on early (< 10) and late (> 20) passages of B16-A melanoma and MN/MCA1 fibrosarcoma. Late passage B16-A cells were Ly-6A/E-negative and refractory to induction of Ly-6A/E (but not of H-2 antigens) by IFN-alpha, IFN-beta, or IFN-gamma; MN/MCA1 maintained a high expression of Ly-6A/E, but no increase was induced by IFNs. It was found that both early and late in vitro passages of MN/MCA1 actively produced IFN-alpha/beta. The analysis of cells of fibroblastic origin revealed a significant correlation between IFN release in the culture medium and Ly-6A/E levels. Culture of fibrosarcoma cells in the presence of an anti-IFN-alpha/beta serum reduced Ly-6A/E expression, thus indicating the existence of an autocrine loop.
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PMID:Ly-6A/E gene is widely expressed among transformed nonhematopoietic cells. Autocrine modulation by interferon. 129 72

The role of combination chemotherapy in the treatment of advanced non-small-cell lung cancer is controversial. At best, a small survival benefit can be achieved. Therefore, other treatment modalities are needed. On the basis of the promising treatment results with interleukin-2 (IL-2) -containing immunotherapy in renal cell cancer and melanoma, we performed a phase I-II study with IL-2 and interferon alpha (IFN-alpha). Eligible patients were treated with IL-2 18 x 10(6) IU/m2/day by continuous intravenous infusion (c.i.v.) for 3 days. On the same days, 5 x 10(6) U/m2/day IFN-alpha was given intramuscularly. After a rest period of 4 days, patients at the first dose level received IL-2 2.4 x 10(6) IU/m2/day c.i.v. for a period of 28 days, followed by 14 days' rest, 14 days' treatment, 7 days' rest, and a final treatment for 14 days. Patients at the second dose level were treated according to the same schedule, in which the dose of IL-2 was increased to 3.6 x 10(6) IU/m2/day. During low-dose IL-2 treatment, patients received IFN-alpha 5 x 10(6) U/m2/day on days 1 and 4 of each week. Eleven patients were admitted to the study, six at the first and five at the second dose level. Median age was 54 years; all patients had a performance status of 0 or 1. The most important adverse effects included anorexia, fatigue, nausea, and headache, which were not dose limiting. In the 11 patients treated, no responses were seen. Nine patients developed progressive disease during the first 5 weeks of treatment. We concluded that this regimen of IL-2 and IFN-alpha is ineffective.
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PMID:Interleukin-2 and interferon-alpha in the treatment of patients with advanced non-small-cell lung cancer. 132 67

Gamma-interferon (gamma IFN) was found to induce expression of the 150,000 M(r) cell surface and the 35,000 M(r) chromatin receptors for nerve growth factor (NGF) in the SW1116 colorectal carcinoma cell line that does not express NGF receptors. In the SW707 colorectal carcinoma cell line that expresses a low level of NGF receptors, gamma IFN stimulated expression of the cell surface and the nuclear receptors. Induction of NGF receptors in SW1116 cells resulted in internalization and nuclear translocation of 125I-NGF. When NGF bound to the chromatin, ribosomal RNA synthesis was inhibited. Two-dimensional gel electrophoresis of [35S]methionine-labeled chromatin proteins indicated significant changes in chromatin protein composition in cells treated and not-treated with gamma IFN. gamma IFN effectively stimulated the expression of NGF receptors in two colorectal carcinoma cell lines, but inhibited the expression in melanoma and breast carcinoma cells. It is suggested that gamma IFN, by modulating the expression of NGF receptors may affect the NGF-dependent growth of some tumor cell lines.
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PMID:Gamma-interferon-induced nerve growth factor receptors in colorectal carcinoma cell lines. 134 Feb 11

Intercellular adhesion molecule-1 (ICAM-1) is involved in cell-cell interactions of leukocytes and parenchymal cells and thus plays an important role in immunologic and inflammatory reactions. The expression of ICAM-1 that is found on many different cells such as melanocytes and melanoma cells is induced by various cytokines, including interferon-gamma (IFN gamma), interleukin (IL)-1 and tumor necrosis factor alpha (TNF alpha). Because expression of ICAM-1 in melanoma was found to correlate with increased risk of metastasis, the regulation of ICAM-1 expression on human melanocytes and melanoma cells was investigated. Foreskin-derived melanocytes and melanoma cell lines (A375, G361) were incubated with different cytokines and ICAM-1 expression was evaluated by fluorescence-activated cell sorter. IFN gamma, IL-1, IL-7, TNF alpha, and TNF beta significantly upregulated ICAM-1 expression in a dose-dependent manner. Most interestingly, the cytokine IL-6, which does not influence adhesion-molecule expression on other cells, significantly upregulated melanocyte and melanoma cell ICAM-1 expression. This effect was dose dependent and could be blocked by an IL-6 antibody. Irradiation with ultraviolet (UVB) light did not influence constitutive ICAM-1 expression on melanoma cells and melanocytes, but suppressed cytokine-induced ICAM-1 expression when cells were harvested 16 h after irradiation. These findings were further confirmed by Northern blot analysis, showing a marked accumulation of ICAM-1 mRNA after cytokine treatment, which was reduced by irradiation with UVB light. However, when UVB-exposed melanoma cells were cultured for at least 48 h induction of ICAM-1 expression was observed. These data indicate that, similar to other cells, ICAM-1 expression on melanoma cells and melanocytes is regulated by cytokines and that UVB light affects ICAM-1 expression on melanocytic cells in a biphasic manner.
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PMID:Modulation of intercellular adhesion molecule-1 expression on human melanocytes and melanoma cells: evidence for a regulatory role of IL-6, IL-7, TNF beta, and UVB light. 134 55

ICAM-1-mediated cell-cell adhesion is essential for various immunologic functions, including non-MHC-restricted cytotoxicity. Shedding of ICAM-1 occurred after stimulation of melanoma cells with TNF alpha and IFN gamma. Soluble forms of ICAM-1 inhibited the conjugate formation of NK clones with K562 and of LAK cells with melanoma cells. Furthermore, the non-MHC-restricted cytotoxicity mediated by NK clones or LAK cells could be abrogated by soluble ICAM-1.
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PMID:[Shedding of soluble intercellular adhesion molecule 1 (ICAM-1) from melanoma cells and the effect on cellular cytotoxicity]. 135 73

A soluble form of the usually membrane-bound adhesion molecule ICAM-1 was detected in supernatants derived from human epidermal keratinocytes. Specifically, supernatants harvested from long-term cultured normal human keratinocytes, or from the spontaneously immortalized keratinocyte cell line HaCaT, did not contain significant amounts of sICAM-1, but shedding of sICAM-1 was found to be markedly induced upon stimulation of keratinocytes with rh IFN gamma. In contrast, cells from the two epidermoid carcinoma cell lines, KB and A431, constitutively shed significant amounts of sICAM-1 even without cytokine stimulation, and sICAM-1 contents in supernatants harvested from these cells were further increased upon stimulation of cells with rh IFN gamma. These studies indicate, that in addition to peripheral blood mononuclear cells and human melanoma cells, human epidermal keratinocytes constitute an important cellular source of sICAM-1. By binding to leukocyte LFA-1 molecules, keratinocyte-derived sICAM-1 may influence inflammatory responses in the skin. In addition, constitutive shedding of sICAM-1 by transformed human keratinocytes may represent a possible mechanism by which neoplastic keratinocytes escape from cytotoxicity.
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PMID:Human epidermal keratinocytes are a source of soluble ICAM-1 molecules. 136 53

Human interferon-alpha A/D (Bg/II) (IFN-alpha A/D) and mouse interferon-gamma (IFN-gamma) are shown to induce xanthine dehydrogenase (XD) mRNA in L929 fibroblastic cells. XD mRNA accumulation after IFN-alpha A/D treatment is relatively fast, being already evident after 4 h and reaching its maximum after 24 h. IFN-alpha A/D is active in inducing XD mRNA at 0.1 unit/ml and it is maximally active at 10(3) units/ml. The half-life of the XD message is unaffected by IFN-alpha A/D treatment, whereas the transcriptional activity of the XD gene and the concentrations of XD heterogeneous nuclear RNA are increased by 2- and 6-fold respectively. The effect of IFN-alpha A/D on XD mRNA is insensitive to cycloheximide, suggesting that protein synthesis de novo is not required. Experiments conducted with specific inhibitors suggest that protein kinase C, cyclic AMP and arachidonic acid metabolites derived from lipoxygenase or cyclooxygenase do not act as second-messenger molecules in the induction of XD mRNA by IFN-alpha A/D. XD mRNA is also induced in NIH3T3 fibroblastic cells, but not in F9 teratocarcinoma or B16 melanoma cells after treatment with IFN-alpha A/D. NIH3T3 are the only cells so far tested that have detectable XD and xanthine oxidase activities under basal conditions and after IFN-alpha A/D treatment, although their responsiveness to the cytokine is much less than that observed in L929 cells.
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PMID:Interferons induce xanthine dehydrogenase gene expression in L929 cells. 137 96

Lymphokine production by human melanoma tumor-infiltrating lymphocytes (TIL) was studied. Uncultured TIL produced interferon gamma (IFN gamma), but not interleukin-2 (IL-2) or IL-4, in response to anti-CD3 mAb or IL-2. In bulk cultures, IL-2-activated TIL displaying autologous tumor-specific cytotoxicity (CTL-TIL) produced IFN gamma in culture with medium alone, whereas IL-2-activated noncytotoxic TIL did not. Addition of anti-CD3 mAb or autologous tumor cells up-regulated IFN gamma production in IL-2-activated TIL from 10 of 12 or 6 of 12 cases respectively. Those from 4 of 12 cases (2 CTL-TIL and 2 noncytotoxic TIL) produced IL-2 in culture with medium alone. At the clonal level, 5 (4 CD4+ and 1 CD8+) of 7 autologous tumor-specific CTL clones derived from TIL and 3 (2 CD4+ and 1 CD8+) of 7 noncytotoxic TIL clones produced IFN gamma in culture with medium alone, which was up-regulated by adding anti-CD3 mAb. Two IFN gamma-producing CTL clones tested produced IL-2 in 4x-concentrated supernatants from a 3.5-h culture with medium alone. Furthermore, 2 IFN gamma-producing CTL clones tested expressed mRNA for both IFN gamma and IL-2. IL-2 production and its mRNA expression were up- or down-regulated, respectively, by adding anti-CD3 mAb or autologous tumor cells. IL-4 production was not observed in culture either with medium alone or with IL-2 in any of the cells described above. Anti-CD3 mAb was required for IL-4 production in 3 of 12 IL-2-activated TIL, 2 of 6 CTL clones, and none of 5 noncytotoxic TIL clones. In summary, IFN gamma production was characteristic of melanoma TIL. Some autologous tumor-specific CTL in TIL are suggested to be productive of IL-2 and IFN gamma under unstimulated conditions, both being required for self-activation in an autocrine loop.
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PMID:Lymphokine production by human melanoma tumor-infiltrating lymphocytes. 138 86

The aim of this phase I study was to exploit the potential efficacy of an alpha-2a-interferon (alpha-2a-IFN)-subcutaneous interleukin-2 (IL-2) combination, bypassing the toxicity usually associated with bolus or continuous infusion of IL-2. Therefore, nineteen patients with metastatic malignancies (7 melanomas, 6 renal cell carcinomas and 6 soft tissue sarcomas) were treated according to a dose escalating schedule of subcutaneous IL-2 combined with intramuscular alpha-2a-IFN for 5 days/week for 3 consecutive weeks. Cycles were repeated every 2-4 weeks unless disease progressed. Alpha-2a-IFN (3 MU/die) was given continuously, including during the rest weeks. IL-2 doses were started at 2 MIU/day/sqm and the MTD of 6 MIU/day/sqm was progressively reached. The dose of IL-2 was given twice daily every 12 hours. Both of the cytokines were administered in an outpatient setting. The main side effects were fever, chills, fatigue, hypotension, nausea and vomiting. Toxicity was correlated with IL-2 dose level. It was found to be mild at 2 and 4 MIU/day/sqm, while, in contrast, grade III toxicity was observed only at the highest dose of 6 MIU/day/sqm. However, this grade III toxicity was manageable and did not prevent continuation of the treatment as long as the dose was not increased above 6 MIU/day/sqm. Three patients, one with melanoma and two with renal cell carcinomas, obtained clinical partial responses. In eight patients, stable disease, and in the remaining eight, progression, were observed. The data suggest that the combined use of the two BRMs has manageable side effects and would seem to be efficacious. A phase II study at the recommended dose of 6 MIU/day is now necessary.
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PMID:An outpatient phase I study of a subcutaneous interleukin-2 and intramuscular alpha-2a-interferon combination in advanced malignancies. 149 78


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