Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bradykinin was found to induce production of IL-6 in human diploid fibroblasts, as well as in a hepatoma-derived cell line, but not in a human melanoma or an osteosarcoma cell line. With the exception of the melanoma cell line, these cells were also found to be responsive to IL-1 beta. The response to bradykinin was faster but less high than that induced by IL-1. Experiments in which IL-1 (-alpha or -beta) and bradykinin were applied simultaneously revealed a synergistic interaction. Of the other cytokines tested, TNF-alpha and IFN-gamma weakly induced IL-6. Neither IL-2, IFN-alpha, nor IFN-beta was able to induce IL-6, either in the absence or the presence of bradykinin. These observations constitute further evidence for the existence of interactions between cytokine and noncytokine peptides, thus linking the neuroendocrine and immune systems.
 ...
PMID:Bradykinin induces interleukin-6 and synergizes with interleukin-1. 193 73

The antiproliferative and antineoplastic effects of the interferons may result, at least in part, from changes in the expression and quantity of specific oncogene products. To explore this hypothesis we have determined the effect of interferons, including recombinant leukocyte (IFN-alpha), fibroblast (IFN-beta) and immune (IFN-gamma), on expression of the Ha-ras proto-oncogene in the human melanoma cell line Colo 38. While concentrations of up to 1000 U/ml of either IFN-alpha or IFN-beta did not affect the total amounts of Ha-ras products, IFN-gamma at concentrations ranging from 20 to 200 U/ml caused a dose- and time-dependent (48-96 hr) reduction (approximately 40%) in the accumulation of Ha-ras-1 mRNA and in the synthesis of the specific protein products. Downregulation of this proto-oncogene occurs prior to the antiproliferative effects of IFN-gamma and parallels similar IFN-gamma mediated changes in the expression of certain melanoma associated antigens. The present findings indicate that this experimental model may prove valuable in determining whether a direct relationship exists between the antiproliferative activity of specific interferons and the downregulation of oncogene expression.
 ...
PMID:Recombinant immune interferon down-regulates Ha-ras-1 proto-oncogene products in a human melanoma cell line. 211 18

In order to identify novel mediators synthesized in activated macrophages, a cDNA library was prepared from cultures of the mouse macrophage cell line RAW 264.7 that had been treated with lymphokine-rich conditioned medium from mitogen-stimulated mouse spleen cells. Differential plaque hybridization identified a cDNA, designated m119, that detected a 1.6-kilobase mRNA that accumulated in response to gamma-interferon (IFN-gamma) but not in response to other macrophage activators, including IFN-alpha, IFN-beta, and lipopolysaccharide. The mRNA encoded a predicted protein of Mr 14,461 containing a 21-amino acid signal peptide. The primary structure of the predicted protein indicated that it is a member of a recently described family of cytokines related to platelet factor 4, including Gro/melanoma growth stimulatory activity and neutrophil-activating peptide/interleukin 8. The selective induction of the m119 mRNA by IFN-gamma that the predicted m119 protein mediates a macrophage activity regulated by IFN-gamma. The m119 protein may be a cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory responses. It is proposed that the gene encoding this protein be called mig, for monokine induced by gamma interferon.
 ...
PMID:A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. 211 67

We have investigated the relationship between in vitro cultivation of autologous melanoma metastases derived from different patients and their levels of expression of class-I and -II major histocompatibility complex (MHC) antigens and melanoma-associated antigens (MAAs). Cell cultures were established from 23 individual metastatic melanoma lesions from 10 patients and were tested early after isolation (between 3rd and 10th passages) for both constitutive expression and modulation by recombinant human leukocyte (IFN-alpha), fibroblast (IFN-beta) or immune (IFN-gamma) interferon of MHC antigens and MAA. All of the melanoma cell lines displayed altered antigen expression following IFN treatment. While in vitro cultures derived from different individuals varied in both constitutive and IFN-modified antigenic expression, cultures of autologous metastases derived from the same patient were very similar. In addition, differences in antigenic profile were apparent when early-passage in vitro cultures were compared with the same melanoma lesion, not established in culture, from which they were derived. The unique de novo and IFN-modified antigenic phenotype of cultures derived from different patients indicates that the antigenic phenotype displayed by melanoma cultures grown in vitro is genetically determined. The differences found between in vitro cultures and their corresponding in vivo lesions, as well as the antigenic heterogeneity displayed by multiple autologous melanoma lesions in vivo, suggest that the in vivo antigenic phenotype may be determined, at least in part, at an epigenetic level.
 ...
PMID:Modulation of the antigenic phenotype of early-passage human melanoma cells derived from multiple autologous metastases by recombinant human leukocyte, fibroblast and immune interferon. 211 85

The human Mx, an interferon (IFN)-alpha- and IFN-beta-induced 76-kd protein, is a homolog (Mx-homolog) to the murine Mx protein, which is necessary and sufficient to provide adequate resistance against influenza virus in murine cells and in mice. Leukocytes from 36 patients with tumors (chronic myelogenic leukemia, hairy cell leukemia, and malignant melanoma) were monitored for their Mx-homolog content before, during, and after rIFN-alpha-2b therapy. Before therapy, only one patient was slightly positive for Mx-homolog. All 36 patients showed a significant increase of Mx-homolog in their mononuclear cells within the first day of IFN therapy. During therapy, the Mx-homolog levels remained elevated. After cessation of treatment, the Mx-homolog content in the mononuclear cells decreased slowly; within 2 weeks, it was about 20-30% of its value during therapy. However, even after 3 weeks, the Mx-homolog was still detectable. The maximally induced Mx-homolog concentration showed a significant correlation to the IFN dose given in vivo. These data indicate that the Mx-homolog is an excellent marker for monitoring the activity of IFN during IFN therapy. In addition, the in vivo endogenous activation of the IFN system might be detectable by the determination of the Mx-homolog despite the lack of circulating IFN.
 ...
PMID:Emergence and decay of the human Mx homolog in cancer patients during and after interferon-alpha therapy. 238 Jul 45

Highly purified interleukin 1 (IL 1) obtained from stimulated human monocytes appeared to be growth inhibitory and cytocidal for a human melanoma cell line, A375. Although IL 1 did not have an immediate cytolytic effect, with time in culture the growth of the target cells was irreversibly inhibited. The cells eventually lysed and decreased markedly in number; the IL 1 effect can therefore be said to be cytocidal. IL 1 activity could not be separated from the cytocidal activity by a variety of chromatography procedures by using conventional and high-performance liquid chromatography (HPLC). The A375 melanoma cell line was also sensitive to another human cytokine alpha-lymphotoxin (alpha-LT) derived from a human B cell line. IL 1 also appeared to be partially growth inhibitory and cytocidal for a LT-sensitive mouse fibroblast cell line, L929; but not for LT-resistant cells, including a subline of L929; a human epithelial carcinoma cell line, HeLa; a human osteosarcoma cell line, HOS; and a mouse SV40-transformed kidney cell line, TU5. However, the LT-sensitive mouse fibroblast cell line, L-M, was resistant to IL 1. Therefore, the cytocidal activity of IL 1 only partially overlapped the target cell selectivity of alpha-LT. Although natural IFN-alpha and recombinant IFN-beta were appreciably growth inhibitory for the A375 cell line, natural and recombinant IFN-alpha and recombinant IFN-beta and IFN-gamma exhibited little cytocidal activity. Purified IL 1 did not have any antiviral activity, and conversely, IFN and alpha-LT were not co-mitogenic for thymocytes. Furthermore, by ELISA and radioimmunoassays, antibodies against human alpha-LT, tumor necrosis factor, and IFN-gamma did not react with IL 1, indicating that IL 1 is antigenically distinct from these other cytokines. These in vitro results suggest that IL 1 may play a role in host defense against some tumors as a cytocidal factor.
 ...
PMID:Human interleukin 1 is a cytocidal factor for several tumor cell lines. 241 93

The effects of IFN-alpha, IFN-beta, and IFN-gamma on the differentiation of murine melanoma cells has been studied, in the presence and absence of melanocyte-stimulating hormone (MSH); the cells were highly responsive to treatment with MSH, which increased the rate of melanin production 25-fold and tyrosinase activity 6-fold within 4 d. Treatment of melanoma cells with IFN-alpha, IFN-beta, or IFN-gamma alone had no stimulatory effect on melanin production, but when the cells were cultured with IFN in the presence of MSH, pigment production was significantly and synergistically increased relative to cells cultured with MSH only. Flow cytometric analysis revealed that levels of tyrosinase in the cells were not affected by MSH or by IFN, which suggests that stimulation of melanogenic activity occurred by activation of a preexisting cellular enzyme. Scatchard analyses showed that the number of MSH receptors on IFN-treated cells was significantly increased (approximately 2.5-fold) relative to untreated cells (approximately 61,000/cell). These findings demonstrate that IFN stimulate differentiation (that is, pigmentation) of melanocytes by increasing the expression of surface MSH receptors; this in turn suggests that such a mechanism may in part be responsible for postinflammatory skin pigmentation, and provides an additional basis for action in the clinical responses of melanoma to IFN treatment.
 ...
PMID:Interferons modulate the expression of hormone receptors on the surface of murine melanoma cells. 246 67

This paper introduces the current status of melanoma treatment with various biologic response modifiers (BRMs) in Japan, with an emphasis on the clinical results of Interferon therapies. The authors also refer briefly to the current situation of interleukin-2 (IL-2) and tumor necrosis factor (TNF) in Japan. Many BRMs have been used in treatment of melanoma, e.g., IFN, IL-2, TNFs, BCG, MY-1 (DNA extracted from BCG), WPG (CWs of Bifidobacterium infantis, ATCC 15697), OK-432 (Picibanil, Streptococcus pyogenes preparation), bestatin, and forphenicinol. Some of these have completed clinical trials, while others are still undergoing clinical testing. Among IFN-alpha, beta, and gamma, intralesional administration of natural IFN-beta was found to be more effective than IFN-alpha for metastatic skin melanoma, the survival time of patients being prolonged by the administration of IFN-beta. IFN-gamma appeared to have lower efficacy than IFN-alpha and beta. The frequency of BRM application to melanoma treatment will increase. The authors foresee that combinations with radio- and/or other chemotherapy will be more common than the single use of a BRM, especially in the case of IFN.
 ...
PMID:Current status of melanoma treatment with interferon, cytokines and other biologic response modifiers in Japan. 246 42

The effect of leukocyte (IFN-alpha), fibroblast (IFN-beta), and immune (IFN-gamma) interferon and/or mezerein on the expression of HLA antigens and melanoma-associated antigens by the melanoma cell line MeWo and its metastatic variant MeM 50-10 was investigated, since this information may contribute to our understanding of the molecular mechanism(s) underlying the metastatic process and of the role of cell differentiation and growth suppression in the antigenic changes induced by interferon (IFN). The three types of IFN had no effect on the expression of high-molecular-weight melanoma-associated antigen, but enhanced that of HLA Class 1 antigens and of intercellular adhesion molecule 1 on MeWo and MeM 50-10 cells. The enhancing effect of IFN-gamma was more marked than that of IFN-alpha and IFN-beta. Furthermore IFN-gamma enhanced the expression of intercellular adhesion molecule 1 by MeM 50-10 cells more than by MeWo cells. IFN-beta was shown for the first time to induce HLA Class II antigens; the effect of IFN-beta, like that of IFN-gamma, is differential on the two cell lines and on the gene products of the HLA-D region. Like IFN-gamma, IFN-beta induced only HLA-DR antigens on MeM 50-10 cells. The results of Northern blot analysis with HLA-DR beta, -DQ beta, and -DP beta probes suggest that the differential modulation of the gene products of the HLA-D region by IFN-beta and IFN-gamma reflects transcriptional and posttranscriptional events. The differential susceptibility to modulation by IFN-beta and IFN-gamma of HLA Class II antigens on MeWo and MeM 50-10 cells is an intrinsic property of each cell line, since only small differences were detected in the number and/or affinity of receptors on the two cell lines. Furthermore, the lack of marked effects of mezerein on the antigen-modulating activity of the three types of IFN, in spite of an enhancement of their differentiating activity, suggests that the changes in the antigenic profile induced by IFN do not represent a differentiation-related phenomenon.
 ...
PMID:Modulation by interferons of HLA antigen, high-molecular-weight melanoma associated antigen, and intercellular adhesion molecule 1 expression by cultured melanoma cells with different metastatic potential. 249 70

Fever is frequently an important side effect of interferon (IFN) therapy. Studies have shown that culturing interferon-treated cells at elevated temperature heightens the antiproliferative activity of IFN-alpha and IFN-beta. Since IFN-gamma has also been shown to be a potent antiproliferative agent, the effect of elevated temperature on IFN-gamma activity was compared to its effect on IFN-alpha and IFN-beta. Mouse B-16 melanoma cells were simultaneously cultured under cloning conditions at a range of temperatures (37.3, 38.1, 38.6, and 39.4 degrees C) in the presence of MuIFN-alpha, MuIFN-beta, and MuIFN-gamma. The antiproliferative activities of all three interferons were enhanced by incubation at the elevated temperatures. However, the elevated temperatures had a more dramatic enhancing effect on the antiproliferative activity of MuIFN-gamma (10-fold enhancement) than of either MuIFN-alpha or MuIFN-beta (2.9- and 3.4-fold enhancement, respectively). Next, the enhancing effect of elevated temperature (39.4 degrees C) was examined for a range of interferon concentrations. The degree of the enhancing effect increased with increasing concentrations of MuIFN-gamma but not with increasing concentrations of MuIFN-alpha or MuIFN-beta. Enhancing effects of temperature as high as 14-fold were observed for 100 units of MuIFN-gamma/ml. This dramatic enhancement was observed for both natural and recombinant MuIFN-gamma and was neither a function of greater relative perception of MuIFN-gamma titer at elevated temperature nor a function of greater relative stability of MuIFN-gamma at the elevated temperature. The differential enhancement of MuIFN-gamma activity by elevated temperature appeared to be specific for the antiproliferative activity, since the antiviral activity of MuIFN-gamma was not relatively more enhanced at 39.4 degrees C than were the antiviral activities of MuIFN-alpha and MuIFN-beta. These results suggest that fever may be an important factor in maximizing the antitumor effects of MuIFN-gamma and perhaps of human IFN-gamma. They also raise the possibility that a combination treatment regimen of hyperthermia and interferon therapy, particularly IFN-gamma therapy, may provide a significant antitumor effect.
 ...
PMID:Effect of hyperthermia on the antiproliferative activities of murine alpha-, beta-, and gamma-interferon: differential enhancement of murine gamma-interferon. 299 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>