UMLS:C0025202 - FACTA Search

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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

The effects of interferon (IFN) on the expression of ICAM-1 in human melanoma cell lines and the shedding of ICAM-1 into spent media were investigated using an indirect binding assay and a double determinant immunoassay (DDIA). While IFN increased the level of expression of ICAM-1 on melanoma cell lines, the susceptibility to IFN differed according to cell line. The enhancing effect of IFN-gamma was concentration-dependent, and it exceeded those of IFN-alpha and IFN-beta. Shedding of ICAM-1 into spent media was detected effectively, and the results agreed well with the expression of ICAM-1 on melanoma cells. Immunostaining of the surgically removed melanoma lesions was positively correlated with the thickness of the primary lesion. The expression of ICAM-1 in primary melanoma lesions was inversely correlated with the disease-free interval. The circulating ICAM-1 with stage 4 melanoma patients significantly exceeded that of stage 1-3 melanoma patients. These observations suggest that ICAM-1 in its soluble form may play an important role in host immunities and may be useful in evaluating the prognosis of patients with melanoma.
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PMID:Analysis of expression and soluble form of intercellular adhesion molecule-1 in malignant melanoma. 128 75

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

Tumor cells often display alterations in their normal program of cellular differentiation. A promising approach for the treatment of cancer involves the induction of terminal differentiation and a loss of proliferative capacity in cancer cells. In human melanoma cells, the combination of mezerein (MEZ) and fibroblast interferon (IFN-beta), results in a rapid and irreversible suppression of cell growth with a concomitant increase in the synthesis of melanin. The induction of terminal differentiation is associated with alterations in the expression of several cellular genes, including fibronectin, ISG-15 and ISG-54, and changes in the expression of specific cell surface antigens, including intercellular adhesion molecule-1 (ICAM-1) and HLA Class I antigens. In the HO-1 human melanoma cell line, induction of terminal differentiation by MEZ plus IFN-beta results in an induction and/or increased expression of ICAM-1, HLA Class I antigens and HLA Class II antigens. IFN-beta and MEZ alone can modulate expression of these antigens to a lower extent than does the combination of compounds. Induction of terminal differentiation and the irreversible suppression of cell growth is not a prerequisite for antigenic modulation in HO-1 cells. This is indicated by the inability of immune interferon (IFN-gamma), a strong inducer of ICAM-1, HLA Class I antigens and HLA Class II antigens synthesis, or the combination of IFN-beta plus IFN-gamma which synergistically but reversibly suppresses HO-1 growth, to induce melanin synthesis or terminal differentiation in HO-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of the antigenic phenotype of human melanoma cells by differentiation-inducing and growth-suppressing agents. 135 50

We assessed natural killer (NK) cell activity against cultured melanoma cells using a novel method, with observations on the comparative effects of interferons (IFNs) in NK-stimulating and anti-proliferative assays. Since the tumour cells tested were adherent, a semi-automated colorimetric MTT dye reduction assay was developed to assess NK activity. The three adherent human melanoma cell lines Sk-Mel-28, MM418 and MM96 were shown to be suitable targets for determining NK activity. Also, these were representative of the range of sensitivities of melanoma cells to the anti-proliferative action of type 1 IFNs. The dose-dependent stimulation of NK activity by type 1 IFNs was confirmed in this alternative assay system. IFN-alpha 2b and IFN-beta ser had equivalent stimulatory activities, and IFN-alpha 4 proved less effective, as with assays using the classical K562 system. Augmented NK cytotoxicity did not correlate with anti-proliferative effects of IFN. In anti-proliferative assays, the hierarchy of activity is IFN-beta greater than IFN-alpha 2 greater than IFN-alpha 4, whereas, in the NK augmentation assay IFN-beta and IFN-alpha 2 were of equivalent activity. Interestingly, MM96 was the cell line most resistant to the direct anti-proliferative action of IFN, yet it was the most susceptible of the melanoma cell lines to cytotoxicity by NK cells, whether stimulated or unstimulated by IFN.
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PMID:Natural killer cell activity against cultured melanoma cells: a dye-reduction technique with studies on augmented activity by interferon subtypes. 138 30

In this study, we evaluated the effect of a series of peripheral-acting benzodiazepines (BZDs), alone and in combination with recombinant human leukocyte (IFN-alpha A), fibroblast (IFN-beta), or immune (IFN-gamma) interferon (IFN), on the growth of human melanoma cells. Specific peripheral-acting BZDs caused a marked suppression in the proliferation of human melanoma cells. The effect on melanoma cell growth required 72 h exposure to the peripheral-acting BZDs and was not observed if the compounds were removed by 48 h. The relative potency of antiproliferative activity of a series of peripheral-acting BZDs on human melanoma cell growth did not correlate with the reported ability of these agents to bind to peripheral sites on the cell membrane of Friend erythroleukemia cells (FELC), nor did they correlate with the ability of these agents to inhibit [3H]thymidine incorporation in FELC, induce differentiation in FELC, or inhibit neurite outgrowth in nerve growth factor-treated rat pheochromocytoma (PC12) cells. The growth of human melanoma cells was also inhibited by various recombinant human IFNs, with IFN-beta displaying greater antiproliferative activity than IFN-alpha A or IFN-gamma. When the peripheral-acting BZD Ro7-3351, which displays growth inhibitory properties when used alone, was combined with IFN, the antiproliferative activity of the combination was greater than either individual compound exerted independently. The combination of IFN-beta plus Ro7-3351 was more active in suppressing HO-1 melanoma cell growth than other IFN preparations in combination with this peripheral-type BZD. Even when combined with a peripheral-acting BZD, such as Ro5-4608, which displayed only marginal antiproliferative activity against human melanoma cells when applied alone, growth suppression of the combination of this peripheral-type BZD with all three types of IFNs was more than additive. These studies suggest that specific peripheral-acting BZDs, both alone and in combination with recombinant IFNs, display novel antiproliferative activity toward human melanoma cells which may involve a different genetic locus than previously observed in other model cell culture systems.
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PMID:Peripheral-acting benzodiazepines inhibit the growth of human melanoma cells and potentiate the antiproliferative activity of recombinant human interferons. 169 6

Twenty-five early-passage (less than or equal to 8) melanoma cell lines, isolated from ten patients with metastatic melanoma, were analyzed by a combination of serological, immunochemical, and molecular methods for mRNA levels, synthesis, and surface expression of MHC class I and class II antigens prior to and following exposure to recombinant human leukocyte (IFN-alpha A), fibroblast (IFN-beta), and immune (IFN-gamma) interferon. All the cell lines expressed variable levels of HLA class I gene products that were up-regulated to different extents upon exposure to specific interferons (IFNs). HLA class II antigens were expressed in 22 of the 25 melanoma lines and IFN-gamma increased the levels of class II mRNA, protein synthesis, and surface expression in all cultures displaying baseline expression. A significant up-regulation of class II antigen expression by IFN-alpha or -beta, associated with higher levels of class II transcripts and enhanced synthesis, was found only in two early-passage human melanoma cell lines. In three lesions from the same patient which did not constitutively express class II antigens, no expression of these glycoproteins could be induced with any of the IFNs. These results indicate that IFN-gamma does not act as a de novo inducer of class II antigen expression in early-passage human melanoma cell lines. This hypothesis is further supported by analysis of class II-associated invariant chain (Ii) expression, which is expressed and induced by IFNs in a manner similar to that of class II antigens. The present study also indicates that early-passage metastatic melanoma lesions from the same patient are heterogeneous in their de novo expression of major histocompatibility antigens and in their modulation by IFNs.
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PMID:Effect of recombinant human leukocyte, fibroblast, and immune interferons on expression of class I and II major histocompatibility complex and invariant chain in early passage human melanoma cells. 170 42

Lymphokine-activated killer (LAK) cells are generated by the incubation of lymphocytes with high levels of interleukin-2 (IL-2). We report here that interferon-gamma (IFN-gamma) acts synergistically with low levels of IL-2 to promote LAK differentiation in peripheral blood lymphocytes as well as in homogeneous T acute lymphocytic leukemic cells exhibiting LAK precursor reactivity. No augmentation of LAK response was observed with IFN-alpha-2, IFN-beta-1, and IFN-beta-2/IL-6. The synergism between IL-2 and IFN-gamma was expressed in the ability of activated lymphocytes to lyse natural killer resistant cell line targets and surgically removed melanoma cells. The augmented LAK response due to IFN-gamma does not reflect up-regulation of the high-affinity IL-2 receptors consisting both of alpha and beta subunits, since expression of the alpha (Tac) subunit on the responding leukemic cells was not increased by IFN-gamma. The observed IFN-gamma/IL-2 synergism in the induction of monoclonal LAK precursors suggests that a single precursor cell responds to both IFN-gamma and IL-2 and that different mechanisms underlie the basal IL-2-mediated LAK response and its enhancement by IFN-gamma.
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PMID:Lymphokine-activated killer (LAK) cells: interferon-gamma synergizes with interleukin-2 to induce LAK cytotoxicity in homogeneous leukemic preparations. 189 16

In an adjuvant clinical trial, 34 high-risk malignant melanoma patients were treated with natural interferon (IFN)-beta and recombinant IFN-gamma. Patients with tumor location on head, neck, and trunk received 3 million IU IFN-beta intravenously (IV) three times weekly for 24 weeks. Patients with tumor location on the extremities received subcutaneous (SC) injection of 2 million IU of IFN-beta distal the locoregional lymph nodes instead. All patients were given 50 micrograms IFN-gamma SC on 3 consecutive days every 4 weeks. Antibody formation was detected by coincubation of IFN and patients' serum and assessment of the inhibition of the cytopathic effect by a virus suspension. Soluble interleukin-2 receptors (sIL-2R) were determined by enzyme-linked immunosorbent assay (ELISA) technique. No antibodies against IFN-gamma were observed. The overall incidence of antibody formation to IFN-beta was 55.8% (19/34). Ninety-two percent of the SC-treated patients (13/14) and 30% (six of 20) of the IV-treated patients developed antibodies. Soluble interleukin-2 receptors were found to be significantly lower in antibody-positive patients than in antibody-negative patients. The authors conclude that IFN-beta antibody formation is frequent and might influence IFN induced sIL-2R elevation in vivo.
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PMID:Formation of neutralizing antibodies against natural interferon-beta, but not against recombinant interferon-gamma during adjuvant therapy for high-risk malignant melanoma patients. 190 14

Sera were collected from 111 patients diagnosed with adenocarcinoma or nonadenocarcinoma malignancies who received different schedules of interferon (IFN)-gamma or IFN-beta ser alone or in combination. Serum carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72) antigen levels were measured to determine whether interferon could enhance the tumor shedding and, thereby, the serum level of either tumor antigen. Less than 10% of the sera samples from patients diagnosed with nonadenocarcinoma malignancies (e.g., hairy cell leukemia, melanoma) had positive titers of TAG-72 or CEA, and interferon neither increased nor resulted in the appearance of either tumor antigen in those sera. In contrast, 59.2% and 75.4% of the patients with adenocarcinoma had positive serum levels of TAG-72 and CEA, respectively, prior to interferon. IFN-gamma and IFN-beta ser alone or in combination significantly increased serum TAG-72 or CEA in approximately 65% of those patients. The results suggest that interferon administration to patients with adenocarcinoma can result in increased serum levels of selected tumor-associated antigens used in the diagnosis of malignancy. These preliminary findings may be important in the development of new strategies to obtain more sensitive tumor antigen serum assays for the diagnosis and monitoring for disease progression of adenocarcinoma.
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PMID:Evidence for the elevation of serum carcinoembryonic antigen and tumor-associated glycoprotein-72 levels in patients administered interferons. 190 81

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