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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

De novo synthesis of major histocompatibility complex (MHC) class II antigens was induced by affinity-purified preparations of interferon (IFN)-gamma, but not by IFN-beta (as judged by the criteria of cell surface expression and protein synthesis) in human osteogenic sarcoma, colorectal carcinoma, and melanoma cell lines that were not constitutive producers of these antigens. The synthesis of heavy-chain and light-chain (beta 2-microglobulin) components of MHC class I antigens was enhanced by both IFN-gamma and IFN-beta; IFN-gamma showed the greater activity. IFN-gamma and IFN-beta also enhanced the expression of class I antigens on the plasma membrane in a dose-dependent manner; IFN-gamma was again the more active agent. Only IFN-gamma induced the membrane appearance of class II antigens in cell lines that appeared negative for HLA-DR expression by all criteria. However, in SW480 cells, which spontaneously express low levels of HLA-DR, IFN-gamma and IFN-beta both enhanced the expression of class II antigens. These results suggest that IFN of both types amplify the products of actively transcribed genes, but that type II IFN is unique in its capacity to induce HLA-DR expression in nonconstitutive cell lines. Kinetic studies showed that enhancement of class I membrane expression preceded the induction of class II expression and peaked earlier. The specificity of these responses was underlined by the inability of either IFN to enhance the synthesis or expression of the tumor-associated membrane glycoprotein gp22. The data indicate that tumor cell lines of diverse tissue origin that do not synthesize or express class II antigens by the criteria of immunoprecipitation or monoclonal antibody binding can be induced to do so by IFN-gamma and may therefore be subject to therapeutic and immunoregulatory modulation.
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PMID:HLA-DR synthesis induction and expression in HLA-DR-negative carcinoma cell lines of diverse origins by interferon-gamma but not by interferon-beta. 392 46

We have analyzed the effects of various human interferons produced in bacteria and the antileukemic compound mezerein (MEZ) on growth and melanogenesis in human melanoma cells. In four human melanoma cell lines, recombinant human fibroblast interferon (IFN-beta) was more active than recombinant human leukocyte interferons (IFN-alpha A, IFN-alpha D, or IFN-alpha A/D (Bgl] in inhibiting cellular proliferation. When monolayer cultures were exposed to 1000 IU/ml IFN-beta for four days the degree of growth inhibition in the different melanoma cell lines varied between 94 and 26%. Similarly, four days growth in medium containing 10 ng/ml MEZ resulted in either no inhibition of growth or as much as 53% inhibition of growth, depending on the specific melanoma cell line tested. MEZ induced dendrite-like processes, cytoplasmic projections morphologically similar to those normally found in neurons and melanocytes, in all four melanoma cell lines, whereas none of the interferons tested had this effect. The combination of interferon and MEZ resulted in a dramatic inhibition in cellular proliferation in all four melanoma cell lines. When cell extracts were assayed for melanin content, a marker of melanoma cell differentiation, the combination of IFN-beta and MEZ resulted in higher levels of melanin than with either agent alone. Dendrite-like formation was also prominent in the cultures treated with this combination. These results indicate that the antiproliferative effect of interferon toward human melanoma dells can be enhanced by treatment with MEZ and that this effect is associated with an enhancement of terminal differentiation.
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PMID:Effects of combined treatment with interferon and mezerein on melanogenesis and growth in human melanoma cells. 398 32

Human blood monocytes, separated on a continuous percoll gradient, were not cytotoxic to allogeneic A375 melanoma cells. The monocyte monolayers were activated to become tumoricidal by incubation for 24 hr with interferon (IFN)-alpha or beta at concentrations of more than 1,000 IU/ml. Significant and reproducible activation of the monocytes was achieved by incubating them with 10,000 IU/ml of IFN-alpha or IFN-beta for 24 hr. Similarly, suspended, but not plated, monocytes were activated to a tumoricidal state by interaction with IFN-alpha or IFN-beta. Monocytes that had lost tumoricidal activity during culture, were reactivated by a second exposure to IFN-alpha. Fluorescence analysis showed that the monocyte-rich adherent monolayers were contaminated with up 2.0% of natural killer (NK) cells. Pretreatment of isolated monocyte preparations with anti-NK cell monoclonal antibody (Leu-11b) to deplete them of NK cell activity did not inhibit the monocyte-mediated cytotoxicity. These results indicate that human monocytes are rendered tumoricidal by direct interaction with IFN-alpha or IFN-beta, although more than 1,000 IU/ml of IFN-alpha or IFN-beta is required for maximal expression of monocyte activation.
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PMID:[Induction of human monocyte-mediated tumor cell killing by alpha or beta interferon]. 399 98

Human blood monocytes, separated on a Percoll gradient, were not cytotoxic to allogeneic melanoma (A375) cells. Fluorescent analysis showed that the monocytes were contaminated with up to 2.0% natural killer (NK) cells. The monocytes became tumoricidal on incubation for 24 h with greater than or equal to 1,000 IU/ml interferon-alpha (IFN-alpha) derived from human lymphoblastic leukemia cells. Anti-IFN-alpha antibody abolished the ability of IFN-alpha to render the monocytes tumoricidal, whereas anti-IFN-beta antibody had no effect. Pretreatment of isolated monocyte preparations with anti-NK cell monoclonal antibodies (Leu-7 and Leu-11b), to inhibit NK cell activity, did not affect the cytotoxicity of IFN-alpha-activated monocytes on tumor cells. Full expression of cytotoxicity on tumor cells required the interaction of monocytes with IFN-alpha for 24 h. These results indicate that IFN-alpha directly activates human monocytes to become tumoricidal, although greater than or equal to 1,000 IU/ml IFN-alpha is required for maximal activation.
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PMID:Induction by interferon-alpha of tumoricidal activity of adherent mononuclear cells from human blood: monocytes as responder and effector cells. 399 64

IFN-gamma is known to induce expression of Ia antigens on a variety of cell types. In the present study, this activity of IFN-gamma has been analyzed with a panel of 36 melanoma cell lines, normal melanocytes, and 97 cell lines representing a range of other differentiation lineages. 55% of the melanoma cell lines express Ia antigens in a constitutive manner without IFN-gamma induction. Of the 16 Ia-melanoma lines, 13 could be induced to express Ia antigens by IFN-gamma, whereas three were noninducible. Melanocytes, which do not normally express Ia antigens, are converted to Ia expression by IFN-gamma. Ia antigens expressed constitutively or after IFN-gamma induction were identified with antibodies detecting monomorphic and allomorphic products of DR and DC loci. IFN-gamma appeared to be unique in its ability to induce Ia expression on melanoma and melanocytes; 14 other agents (including IFN-alpha and IFN-beta) known to influence growth or differentiation did not have Ia-inducing activity. Equally striking is the restriction of antigenic changes following IFN-gamma induction to HLA-associated products; of the 38 systems of cell surface antigens examined, only HLA-A,B,C, beta 2m, and Ia antigens were affected. A variety of other Ia- cell types were shown to be Ia-inducible by IFN-gamma; these included established lines of breast, colon, pancreas, bladder, kidney, ovary, and brain cancers, and cultures of normal fibroblasts, kidney epithelia, and epidermal keratinocytes. In contrast, three tumor types, teratocarcinoma, choriocarcinoma, and neuroblastoma, were not inducible for Ia expression, even though IFN-gamma could induce expression of HLA-A,B,C products. The broad representation of Ia antigens on most somatic cell types expressed either constitutively or after IFN-gamma can be viewed in an immunological context (antigen presentation/immune regulatory signals) or could indicate that Ia products have functions other than those related to immune reactions.
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PMID:Surface antigens of melanoma and melanocytes. Specificity of induction of Ia antigens by human gamma-interferon. 620 1

The antiviral and antiproliferative effects of highly purified Escherichia coli-derived human interferons (IFNs) were examined in human melanoma cells (Hs294T). Antiproliferative activity was monitored by measuring inhibition of cell multiplication, and antiviral activity was determined by inhibition of herpes simplex virus type 1 replication. Treatment of cells with IFN-gamma in combination with IFN-alpha A or IFN-beta 1 resulted in potentiation of both antiproliferative and antiviral activities. In contrast, combination treatments composed of IFN-alpha A and IFN beta 1 yielded inconsistent results. Some combinations reflected additive responses, whereas others were antagonistic. To examine correlations between IFN-induced biological activities and interactions of the different IFNs with cell surface receptors, in vivo [35S]methionine-labeled IFN-alpha A was prepared. Binding studies indicated the presence of 2,980 +/- 170 receptors per cell, each with an apparent Kd of (8.4 +/- 1.3) X 10(-11) M. Results from competitive binding studies suggested that Hs294T cells possess at least two types of IFN receptors: one which binds IFN-alpha A and IFN-beta 1 and another to which IFN-gamma binds.
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PMID:Synergistic antiviral and antiproliferative activities of Escherichia coli-derived human alpha, beta, and gamma interferons. 631 48

The ability of recombinant interferon-gamma (IFN-gamma) to activate mouse macrophages was investigated. The use of recombinant IFN-gamma has the advantage of being devoid of contaminating lymphokines. Two preparations of IFN-gamma were utilized, one which was not glycosylated and which was highly purified from Escherichia coli another which was glycosylated and which was from transfected COS-7 monkey cells. Both preparations of recombinant IFN-gamma activated murine macrophages to kill lymphoma and melanoma tumor targets, suggesting that glycosylation of the protein or the presence of other mammalian proteins is not essential for activation. Significant levels of cytolytic activity were induced from IFN-gamma (1 to 10 units/ml). This activity was undiminished by treatment of the IFN-gamma preparations with polymixin B at doses which neutralized endotoxin (50 micrograms/ml). Similarly, IFN-gamma, at low concentrations, induced an inhibition of migration by macrophages. Based on antiviral activity, IFN-gamma was shown to be 100 to 1000 times more potent than was IFN-beta as a macrophage-activating agent. Taken together, these results demonstrate that murine IFN-gamma is a macrophage-activating factor which is effective at physiological concentrations. Of particular interest is the observation that the nonglycosylated E. coli-derived IFN-gamma is active and therefore may be of value for therapeutic studies, since it can be easily produced in large amounts.
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PMID:Potent activation of mouse macrophages by recombinant interferon-gamma. 643 14

For the determination of the conditions for the most effective cytolysis of human melanoma cells, leukocyte interferon (IFN-alpha), fibroblast interferon (IFN-beta), and immune interferon (IFN-gamma) were compared for their abilities to kill cultured human melanoma cells in the presence and absence of peripheral blood mononuclear leukocytes (PBL). A microassay was employed in which the viability of melanoma target cells was determined after various times of incubation with interferons alone or with PBL. On 7 human melanoma cell lines (from 6 different patients), IFN-gamma had significantly greater direct anticellular effect than IFN-alpha or IFN-beta. When PBL were added, all target cells were killed after 48 hours with IFN-gamma, but they were not killed with IFN-alpha or IFN-beta. When IFN-gamma was added to either IFN-alpha or IFN-beta, a potentiation of the anticellular effect was observed both with and without PBL. The actions of this "natural" IFN-gamma could be reproduced with recombinant IFN-gamma and could be neutralized by an antibody to a synthetic peptide encoded by the 5'-end of IFN-gamma complementary DNA. It was concluded that IFN-gamma is significantly more active against these human melanoma cell lines than either IFN-alpha or IFN-beta and, most significantly, that eradication can occur in the presence of IFN-gamma and PBL. Furthermore, synergistic anticellular action can be observed when IFN-gamma is added to IFN-alpha or IFN-beta. These findings point to the need for preclinical trials to evaluate eradication in vivo.
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PMID:Eradication of cultured human melanoma cells by immune interferon and leukocytes. 643 63

When human alveolar macrophages (AM) obtained by lavage of the lungs of healthy donors were incubated in medium with or without lipopolysaccharide (LPS) they released a factor(s) with tumor cell killing activity. This tumor cytolytic and/or cytotoxic factor(s) (TCF) was assayed by measuring its effect in inhibiting target cell growth. TCF activity was not observed in the supernatant from cultures of LPS-treated hematopoietic malignant cell lines (monocytic leukemia, B-cell leukemia and T-cell leukemia cell lines). Human TCF was significantly cytotoxic to 13 of 15 solid-tumor cell lines tested and to 7 of 9 hematopoietic malignant cell lines, but not to two different normal, nontumorigenic cell lines. TCF-rich supernatants contained low levels of interferon (IFN) activity that were not significantly cytotoxic to A-375 melanoma cells. Human TCF and IFN-alpha or IFN-beta had additive cytotoxic effects. These data suggest that human TCF released by activated human AM may be of potential use in the treatment of malignant disseminated diseases.
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PMID:In vitro cytotoxicity to various human tumor cell lines of a tumor cytotoxic factor(s) produced by human alveolar macrophages. 643 93

16 patients with skin metastases of malignant melanoma were treated by intratumoral administration of human fibroblast interferon (Hu IFN-beta), with remarkably gratifying results. Generally, the antitumor effect became evident early in the course of treatment. Of particular interest are the histopathologic findings in the malignant lesions. In response to intratumoral injection of Hu IFN-beta, a strikingly large number of lymphocytes emerged to surround and infiltrate into the tumor, not only causing dissociation of its architecture but often surrounding the tumor cells. After a few intratumoral doses, the tumor cells were completely replaced by an abundance of lymphocytes with subsequent emergence of macrophages. These reactions were suggestive of lymphocyte cytotoxicity of killer T cells. By transmission and scanning electron microscopy, the same finding as light microscopy are observed.
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PMID:[Clinical effect and histopathologic observation of malignant melanoma by intratumoral administration of HuIFN- beta]. 687 28


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