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)

Human blood monocytes from healthy volunteers, separated by centrifugal elutriation, were not cytotoxic to allogeneic A 375 melanoma cells. The monocytes were rendered tumoricidal by incubation for 24 h with natural interferon-alpha and beta or recombinant interferon-alpha A and alpha A/D (more than 100 U/ml) or with interferon-gamma (more than 1 U/ml). Liposome-MTP-PE at concentrations of more than 50 nmol/ml also induced tumoricidal activity of monocytes. When a combination of subthreshold concentrations of these IFNs and liposome-MTP-PE were added to monocyte cultures, IFN-alpha and beta acted additively in monocyte activation, while IFN-gamma acted synergistically. The synergism for monocyte activation required that monocytes be incubated first with IFN-gamma and then with liposome-MTP-PE. These findings suggest that the synergistic effect of IFN-gamma and liposome-MTP-PE can decrease the necessary clinical doses of these agents for malignant diseases, and may have therapeutic availability in the treatment of metastatic cancer in humans.
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PMID:[Induction of tumoricidal properties in human monocytes by synergism between interferon-gamma and liposome-entrapped muramyl tripeptide]. 309 16

The regulatory effects of human recombinant and hybrid interferons-alpha (IFN-alpha) on macrophage-mediated tumoricidal activity were examined. Recombinant hybrid IFN-alpha-A/D suppressed the capacity of murine interferon-gamma (IFN-gamma) to activate mouse peritoneal macrophages to a tumorilytic state, and blocked the killing of syngeneic syngeneic melanoma target cells by macrophages previously committed to the cytotoxic phenotype with a 4-h pretreatment with IFN-gamma. This suppressive activity was limited to IFN-alpha-A/D, as IFN-alpha-A and IFN-alpha-D were not effective. In contrast, IFN-alpha-A, -D, and -A/D were all capable of activating human peripheral blood monocytes to lyse human tumor cells. When encapsulated in liposomes, only IFN-alpha-A/D maintained its monocyte activating efficacy. These findings suggest that the immunomodulatory effects of IFN-alpha subtypes and hybrid molecules are dependent on species of monocytes/macrophages, subtype, and nature of presentation to effector cells.
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PMID:Regulatory effects on macrophages of human recombinant interferons-alpha. 310 Jun 67

Class I and II histocompatibility antigen expression was studied in cryostat sections of biopsy tissues from 15 patients diagnosed as suffering from malignant melanoma, using monoclonal antibodies against HLA class I and II monomorphic determinants and an indirect immunofluorescence technique. Class I antigens were detected in three of the four primary melanomas and in five of the eleven metastatic melanomas. Class II antigens were expressed only in metastatic melanomas, in three out of eleven cases. Some tumour cell suspensions were obtained and short-term cultures were established. Radiobinding and immunoprecipitation studies were carried out in two cases, named M6 and M8. The results were comparable to those obtained with direct immunofluorescence. We modulated the expression of class I and II HLA antigens with interferon in M6 when adapted to tissue culture. This melanoma was class I and II negative; after IFN gamma treatment it became strongly positive for class I and II antigens. In addition we have demonstrated, using Southern blot analysis with the restriction enzymes PvuII and EcoRI, that the M6 melanoma does not have any detectable alterations in its class II beta genes.
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PMID:Differential expression of HLA class I and II antigens in primary and metastatic melanomas. 310 17

The antitumor effects of murine recombinant interferons (beta) and (gamma) against B-16 melanoma and B16-F10 melanoma were examined. In a pharmacokinetic study, intraperitoneal injection of Mu-rIFN (gamma) produced higher and longer detectable IFN activity than administration of Mu-rIFN (beta) in both plasma and organs. In clonogenic assay, Mu-rIFN (gamma) at 1,000 units/ml showed 80% inhibition of colonies of B16-F10 melanoma. However, Mu-rIFN (beta) hardly inhibited the colony formation of B16-F10 melanoma. Furthermore, both IFNs had different characteristics from each other in the augmentation of NK cell and macrophage activities. In the experimental metastasis of B-16 melanoma, the inhibitory effect of Mu-rIFN (beta) on the pulmonary metastasis was mediated by the host defense mechanism, and NK cells and macrophages were important for the inhibition. Mu-rIFN (gamma) showed a stronger effect against B16-F10 melanoma in the inhibition of the growth of sc implanted tumor and artificial metastasis.
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PMID:[Direct and indirect antitumor effect of murine recombinant interferons]. 310 63

A total of 30 patients with progressively growing visceral and/or cutaneous malignant melanoma metastases were entered in a prospective phase II trial comparing three different therapeutic regimens of recombinant interferons (r-IFN). The first group of 12 patients received r-IFN alpha A 9-36 IU/day i.m. on 5 consecutive days/week. A second group of 11 patients was treated with r-IFN alpha A and oral cimetidine, 1000 mg/day. The third group of 7 patients had i.v. infusions of r-IFN gamma 0.25-0.5 mg/m2 on 3 days/week. Of the 12 r-IFN alpha A-treated patients, 1 responded (complete response, CR), 5 patients exhibited no change (NC), 3 patients had progressive disease (PD), and 3 patients could not be evaluated after therapy. In the group treated with r-IFN alpha A plus cimetidine 3 patients responded (1 CR, 2 partial responses) and 3 exhibited NC. The remaining patients showed PD. Treatment responses were found exclusively in patients with cutaneous and/or lymph node metastases. In contrast, none of the r-IFN gamma-treated patients responded to therapy. Known IFN side effects of varying degrees, sometimes severe, were observed in all patients. Despite the small numbers of patients treated, our preliminary data indicate that r-IFN alpha A therapy seems (1) to be of some therapeutic value in the treatment of cutaneous melanoma metastases, (2) to be superior to r-IFN gamma therapy, and (3) that overall response rates improve with the addition of oral cimetidine to r-IFN alpha A treatment.
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PMID:Comparison of the effects of three different treatment regimens of recombinant interferons (r-IFN alpha, r-IFN gamma, and r-IFN alpha + cimetidine) in disseminated malignant melanoma. 311 65

To develop monoclonal antibodies (mAb) recognizing human melanoma-associated antigens (MAA) susceptible to modulation by immune interferon (IFN-gamma), hybridomas were constructed with splenocytes from a BALB/c mouse immunized with IFN-gamma-treated melanoma cells Colo 38. Screening of supernatants with control and IFN-gamma-treated melanoma cells showed that the mAb CL203 and CL207 display preferential reactivity with IFN-gamma-treated melanoma cells. The two mAb recognize the same (or spatially close) determinant on a 96,000 MAA which has a density of 0.36 X 10(6) antigenic sites/cell on untreated melanoma cells Colo 38 and of 1.39 X 10(6) and 1.54 X 10(6) on melanoma cells Colo 38 treated with IFN-gamma (final concentration, 200 U/ml) for 24 and 48 hr, respectively. The effect of IFN-gamma on the 96,000 MAA is dose- and time-dependent, reversible, and blocked by inhibitors of RNA and protein synthesis. Furthermore, the effect of IFN-gamma on the induction of the 96,000 MAA appears to be specific, inasmuch as IFN-alpha and IFN-beta do not induce the expression of the 96,000 MAA. The latter is also induced by IFN-gamma in a variety of carcinoma cell lines, but its level is markedly lower than on melanoma cells. Furthermore, the apparent m.w. of the antigen synthesized by the carcinoma cell lines in the presence of IFN-gamma ranges between 93,000 and 96,000. This molecular heterogeneity appears to reflect differences in the degree of glycosylation of the polypeptide moiety because the antigen synthesized by a variety of cell lines in the presence of tunicamycin has an apparent m.w. of 51,000.
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PMID:Characterization of a monoclonal antibody-defined human melanoma-associated antigen susceptible to induction by immune interferon. 311 85

The relationship between major histocompatibility complex (MHC) antigens and metastasis was investigated on B16 melanoma variants. B16 cell lines express low amounts of murine MHC (H-2) antigens. A high expression can be induced in line B16-A by in vitro treatment with immune interferon (IFN-gamma) or by in vivo transplant in allogeneic mice. The increase of H-2 antigens correlated with an enhancement of lung colonization in young syngeneic mice. The higher metastatic capacity of B16-A cells with induced high levels of H-2 antigens was observed also in adult mice and in young mice pretreated with cyclophosphamide. These results were confirmed investigating the behaviour of a mutant B16 clone (B78H1) which was selectively resistant to the H-2-inducing action of IFN-gamma: lung colonization ability was not increased by IFN pretreatment. The study of variants derived from individual B16-A lung colonies revealed a wide range of H-2 levels. Variants with a low expression had a low colonization ability; one out of two variants with a high H-2 expression also was poorly colonizing. IFN-gamma-mediated H-2 expression appeared to act as an enhancer, rather than a determinant of B16 metastatic capacity.
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PMID:Interferon-mediated enhancement of metastasis. Are MHC antigens involved? 311 68

Interferon treatment has been shown to cause myelosuppression in man and in a mouse model. Combinations of interferon-gamma (IFN-gamma) with either interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta) cause the synergistic enhancement of interferons' antiviral, antiproliferative, antitumor, and immunoregulatory activities. Thus, combinations of MuIFN-beta and either natural or recombinant DNA-derived MuIFN-gamma were evaluated for their ability to cause the synergistic enhancement of interferon's myelosuppressive activity. The combinations of interferons were evaluated in vitro in bone-marrow colony-stimulating assays. They were seen to potentiate the in vitro myelosuppressive effect of the interferons. The combinations were evaluated for their in vivo myelosuppressive effect in mice. Treatment with the separate interferons caused a significant reduction in the number of circulating leukocytes, suggesting a potent myelosuppressive effect. However, treatment with the interferons in combination caused an antagonism and led to a myelosuppressive effect which was no greater than that of the interferons alone. The combinations of interferons were employed at concentrations which have been shown to provide substantial potentiation of the antitumor action of the interferons against B-16 melanoma. Thus, the data suggest that combination interferon therapy employing IFN-gamma together with either IFN-alpha or IFN-beta provide a potentiated antitumor activity without increasing the myelosuppressive side effect of the therapy.
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PMID:In vivo myelosuppression by combination interferon treatment: antagonism of MuIFN-gamma and MuIFN-beta myelosuppressive effects. 311 81

The effects of a combination of recombinant alpha-interferon (IFN-alpha) and interleukin-2 (IL-2)-activated human killer cells (lymphokine-activated killer or LAK cells) on Hs294T (IFN-sensitive) and A375P (IFN-resistant) human melanoma cell lines were evaluated. Pretreatment of target cells with IFN-alpha for at least 1 day increased their susceptibility to the lytic activity of LAK cells. The combination of the two agents in sequence (IFN-alpha followed by LAK cells) resulted in a true synergystic killing of both IFN-alpha-sensitive and resistant tumor cells. No synergy was observed when the sequence was reversed (LAK cells followed by IFN-alpha). When peripheral blood mononuclear cells were incubated simultaneously with IFN-alpha and IL-2, LAK cell generation and antitumor activity was markedly inhibited when tested against both IFN-treated and -non-treated tumor cells. These studies may be used to plan clinical trials of combination cytokine therapy for human cancer.
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PMID:Synergism between alpha-interferon and interleukin-2-activated killer cells: in vitro studies. 312 52

The sensitivity of H-2b-high and H-2b-low variants of BL6 melanoma to the cytotoxic action of NK and lymphokine-activated killer cells was investigated. BL6 mouse melanoma cells lack detectable H-2Kb and had low levels of expression of H-2Db Ag. The BL6T2 variant cells, obtained after treatment of BL6 cells with mutagen N-methyl-N-nitro-N'-nitro-soguanidine, had relatively high levels of expression of class I H-2b Ag. Poly(I:C)-stimulated spleen cells of nude mice were highly cytotoxic for BL6T2, whereas H-2b-low BL6 cells were less sensitive to NK activity in an 18-h 51Cr-release assay. Similar results were obtained after 4-h incubation of radio-labeled tumor cells with IL-2-activated effector cells. In contrast, both lines were equally sensitive to lysis by purified granules derived from rat large granular lymphocytes (LGL) or by macrophages. By using various clones selected from BL6 or BL6T2 cells, it was found that BL6 or BL6T2 clones with low H-2b Ag expression were less sensitive to lysis by NK cells than H-2b-high clones. After IFN treatment of either BL6 or BL6T2, the target cells became more resistant to lysis by either NK cells or by purified LGL granules. IFN-treated BL6 cells had substantially increased expression of H-2b Ag and in this respect became similar to untreated BL6T2. However, IFN-treated BL6 cells were more resistant than BL6T2 cells to lysis by NK cells and LGL granules, suggesting that augmentation of H-2b Ag expression and NK resistance could be two independent IFN-induced effects. With a cold target inhibition assay, it was found that BL6T2 or its H-2 positive clones were highly competitive and inhibited the cytotoxic activity of NK and lymphokine-activated killer cells against radiolabeled YAC-1 and BL6T2, whereas BL6 cells or H-2-negative clones of BL6T2 and BL6 lines showed poor competitive ability. Thus, our data indicate that the NK resistance of H-2-low BL6 cells may be due to a paucity of NK recognizable determinants. N-Methyl-N-nitro-N'-nitroguanidine treatment of BL6 melanoma cells was associated with an increase in class I H-2b Ag expression and NK sensitivity, suggesting the involvement of class I MHC Ag in the sensitivity of tumor cells to NK cell-mediated cytotoxicity.
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PMID:H-2 antigen expression and sensitivity of BL6 melanoma cells to natural killer cell cytotoxicity. 312 40


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