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

The clinical and immune modulatory effects of interleukin-2 (IL-2) and interferon (INF) alfa-2a were examined in a phase II study in patients with metastatic renal cell carcinoma (six patients) and melanoma (eight patients). Treatment consisted in IL-2 3 MU/m2 continuous infusion days 1-4 and INF alfa-2a 6 MU/m2 subcutaneously day 1 and 4, both given on alternate weeks. Tumour response was assessed after four cycles of treatment or earlier, if necessary. Patients with stable disease or response were to be continued for another nine cycles or up to disease progression. The 14 patients received a total of 60 cycles of treatment. Major toxicities (WHO Grade III/IV) were fever, capillary leak syndrome with hypotension, nausea and vomiting, erythema with pruritus, leuco- and thrombopenia and sepsis with staphylococcus aureus. Five of 14 patients (36%) developed a self limiting autoimmune thyroiditis with HLA-DR expression on thyrocytes. Long term treatment toxicity was moderate with an average weight loss of 5% and an average fall in Karnofsky index of 10% compared to baseline. No responses were seen in renal cell carcinoma, two patients with melanoma had a partial and two a minor response with a duration of 1-7 months. Serial measurements of immune modulatory parameters showed a functional response to treatment with an increase of NK- and LAK-activity during the first two cycles, followed by a plateau and decrease during the third and fourth cycles. These findings were paralleled by a successive decline in treatment induced INF gamma response. These findings suggest, that alternative weekly treatment with IL-2 and INF alfa-2a results in an exhaustion of lytic capacity of NK- and LAK-cells and an attenuation of secondary cytokine release.
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PMID:Clinical and immune modulatory effects of alternative weekly interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma. 199 8

To determine whether isolates of Plasmodium falciparum have intrinsically different cytoadherent properties and whether these differences contribute to the clinical severity of human falciparum malaria, we studied the cytoadherence to C32 melanoma cells in vitro of 59 parasite isolates from patients with naturally acquired infections in Thailand. Parasitized erythrocytes adhere to these melanoma cells principally via the glycoprotein CD36, which is also expressed on most vascular endothelium. In vitro cytoadherence was significantly greater for isolates from patients with biochemical evidence of severe malaria. The cytoadherent properties of P. falciparum parasites may thus be a virulence factor in human falciparum malaria. However, there was no correlation between the degree of in vitro cytoadherence and cerebral symptoms, which suggests that other receptors and/or host factors may be important in the adherence of malaria parasites to cerebral vascular endothelium. The cytokines tumor necrosis factor, interleukin-1, and gamma interferon, which have been implicated in the pathogenesis of cerebral malaria and are known to promote intercellular adhesion in other systems, did not enhance the cytoadherence of P. falciparum isolates to C32 melanoma cells.
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PMID:Clinical correlates of in vitro Plasmodium falciparum cytoadherence. 199 37

The administration of recombinant human macrophage colony-stimulating factor (M-CSF) i.p. in doses of 25 or 100 micrograms twice daily for 5 consecutive days to non-tumor-bearing C57BL/6 mice resulted in a dose-dependent infiltration of mononuclear cells in the livers but not the lungs of these treated animals. Immunohistochemical examination of fixed liver tissue with the murine macrophage-specific monoclonal antibody, F4/80, revealed a greater than 5-fold increase in the number of hepatic macrophages. Quantification of F4/80-positive cells in a mononuclear single cell suspension derived from liver revealed a greater than 25-fold expansion in the number of hepatic macrophages compared to control mice. These cells were then tested in 18-h 51Cr release assays for tumoricidal activity, after an 18-h incubation with or without gamma-interferon, against cultured P815 targets. Significant tumor cell lysis by these liver-associated mononuclear cells occurred, which was enhanced by gamma-interferon preincubation. The systemic administration of M-CSF alone at high dose had no antitumor impact in vivo against 3-day pulmonary metastases from the MCA-203 sarcoma and B16 melanoma or hepatic metastases from the B16 melanoma or MCA-105, -203, or -207 sarcomas. Although the systemic administration of M-CSF in combination with tumor-specific monoclonal antibody had no effect on 3-day pulmonary metastases from the B16 melanoma, significant reductions in liver metastases were seen. These murine studies demonstrate the biological activity of recombinant human M-CSF in vivo and suggest that the administration of this cytokine in combination with specific monoclonal antibody may be useful in the treatment of patients with metastatic disease at sites of monocyte/macrophage accumulation.
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PMID:Biological and antitumor effects of recombinant human macrophage colony-stimulating factor in mice. 202 43

We determined whether the presence of phosphatidylserine (PS) in the outer membrane leaflet of human tumor cells correlated with their recognition by activated human monocytes. Three tumorigenic cell lines, A375 melanoma and A431 and Colo-16 carcinomas, and a normal human epidermal keratinocyte line (NHEK) were incubated with monocytes activated to the tumoricidal state by gamma-interferon and lipopolysaccharide. Activated human monocytes bound to and lysed all tumorigenic targets, while the nontumorigenic NHEK were neither bound nor killed. Semiquantitative analysis of PS in the outer leaflet of the cells revealed that the tumorigenic cells expressed 3-7-fold more PS than did the nontumorigenic NHEK. To determine whether enhanced PS expression on the tumor cells was responsible for their recognition by activated monocytes, NHEK were supplemented with exogenously supplied analogues of PS and phosphatidylcholine. PS-labeled NHEK but not phosphatidylcholine-labeled nor control NHEK bound to activated human monocytes. These results suggest a role for PS in monocyte recognition of tumor cells.
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PMID:Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes. 203 47

Advanced cancer responds clinically to combined therapy with recombinant interferon-alpha and 5-fluorouracil. Although the two agents may interact in the biosynthetic pathway for thymidine, we investigated, as an alternative mechanism, the regulation of susceptibility of the A375 human melanoma to natural killers activated by interferon. A375 were preincubated with 5-fluorouracil, interferon, or both sequentially prior to assay as targets for cell-mediated killing. Pretreatment of A375 with interferon decreased apparent lytic efficiency. 5-Fluorouracil alone increased the susceptibility of A375 to killing. Pretreatment of targets with 5-fluorouracil abrogated the resistance normally induced by interferon pretreatment. Thus, 5-fluorouracil modulates certain immunoregulatory effects of interferon-alpha. Thymidine does not block the effect of 5-fluorouracil. While fluorodeoxyuridine is relatively ineffective in this system, fluorouridine is more effective than 5-fluorouracil in abrogating the effect of interferon. These data suggest important interactions of 5-fluorouracil and interferon in pathways for protein synthesis. It is known that interferon both increases the activity of natural killers and increases resistance of tumors to natural killers. We have shown that 5-fluorouracil, by blocking the resistance, may allow the augmented natural killing to be effective. This observation provides an alternate hypothesis for the clinical activity of 5-fluorouracil and interferon in combination.
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PMID:Abrogation of interferon-induced resistance to interferon-activated major histocompatibility complex-unrestricted killers by treatment of a melanoma cell line with 5-fluorouracil. 203 94

Sixty-four patients with histologically confirmed metastatic malignant melanoma were entered on a prospectively controlled randomized trial. Patients received dacarbazine (DTIC) alone or DTIC plus interferon (IFN) alfa-2b. Patients were reasonably balanced with respect to age, sex, performance status (PS), site of metastases, and number of metastatic sites. Objective response (complete plus partial remission [CR + PR]) was documented in six patients on DTIC and in 16 patients on DTIC plus IFN alfa-2b. Median time to treatment failure (TTF) and median survival are significantly better on the combination arm, with some long-term CRs observed. More toxicity was encountered in the combination arm, which was acceptable except in three patients where treatment was discontinued because of IFN toxicity.
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PMID:Improved results with the addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. 207 44

To determine whether recombinant human alpha-interferon (rIFN alpha A) could enhance tumor uptake of an antimelanoma monoclonal antibody (Mab) 96.5 in vivo, groups of nude mice bearing P97 antigen-positive human melanoma subcutaneous xenografts were given i.m. injections of normal saline or rIFN alpha A daily for 10 days. On day 7, mice received either 5 micrograms of 111In-labeled Mab 96.5 or irrelevant 111In-labeled subclass-matched or non-subclass-matched control Mabs. Animals were killed 72 h later and the percent injected dose per gram (%ID/g) in tumor and normal organs was determined. There was a significant (p less than 0.001) increase in 96.5 in tumors of IFN-treated mice compared to saline-treated mice and mice receiving irrelevant Mabs. There was also a significantly increased uptake of 96.5 in blood, heart, lung, kidney, and muscle of IFN-treated vs. control mice (p less than 0.05). This finding was most likely due to increased antigen shedding since significant differences in %ID/g were not observed between IFN-treated and control mice bearing antigen-negative tumors. Furthermore, P97 content in tumor and tissues of IFN-treated mice bearing melanoma xenografts was significantly higher than in mice without tumors. In summary, IFN enhanced targeting of 96.5 via an antigen-specific mechanism. These data confirm and extend previous studies in other tumor systems, and suggest that clinical trials of Mabs plus IFN might be useful in overcoming poor Mab localization that occurs as a result of antigenic heterogeneity in humans.
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PMID:Recombinant alpha-interferon enhances tumor targeting of an antimelanoma monoclonal antibody in vivo. 207 42

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.
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PMID:A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. 211 67

Interferon treatment increases the ability of tumour cells to colonize the lungs. Although it has been suggested that this effect can be explained by increases in the expression of MHC molecules the precise mechanism is still uncertain. The growth in the lungs of a low (F1) and a high colonizing variant (BL6) of the B16 mouse melanoma have been studied after in vitro treatment with interferon. Interferon-gamma, but not interferon-alpha/beta, increased the number of lung colonies formed after intravenous injection, but not after subcutaneous administration. Treatment also increased the sizes of the lung colonies formed and the number of radiolabelled cells retained by the lungs. However, no clear relationship was observed between the number of colonies formed and the concentration of interferon used. The effect of interferon on F1 was greater than on BL6, but the overall number of colonies formed was very similar. These results suggest that interferon increases the adhesiveness of these cell lines in a fairly non-specific manner, that seems unlikely to involve MHC molecules. As a results of this and other studies the importance of interferon in the process of tumour spread seems very questionable.
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PMID:A detailed study of the effects of in vitro interferon treatment on the growth of two variants of the B16 mouse melanoma in the lungs: evidence for non-specific effects. 211 16

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.
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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


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