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)

beta-All-trans-retinoic acid (RA) has been shown to inhibit the growth, enhance the differentiation, and suppress the transformed and metastatic properties of certain human and murine melanoma cells. This study examined the effect of RA on the level of a cell surface receptor (M(r) 78,000) (gp78) for an autocrine motility factor, which has been implicated in invasion and metastasis. Treatment of murine melanoma cell lines S91-C2, B16-F1, and K1735-P with RA (10 microM) for 5 days decreased the level of gp78 by 37, 72, and 92%, respectively, as revealed by immunoblotting with monoclonal antibodies raised against gp78. In contrast, RA had only a limited effect on gp78 levels in melanoma cell clones or variant cell lines that are resistant to the growth-inhibitory effects of RA (S91-C154, B16-F10, and K1735-Cl19). Further studies with K1735-P, the most sensitive cell line with respect to modulation of gp78, showed that the decrease in gp78 level required at least 1 microM RA and 4 to 5 days of treatment. The binding of anti-gp78 antibodies to the surface of intact RA-treated cells and to intracellular gp78 in permeabilized cells was also lower than in untreated cells. Furthermore, RA treatment decreased the induction of cell motility, on colloidal gold-coated glass coverslips, by anti-gp78 antibodies, which mimic the effect of autocrine motility factor. The RA-induced decrease in antibody-enhanced cell motility was similar to the time- and RA concentration-dependent decrease in the amount of gp78, suggesting that the two events are related. These results raise the possibility that the previously reported suppression by RA of tumor cell invasion and metastasis may be related, at least in part, to suppression of cell motility resulting from the decreased level of the autocrine motility factor receptor.
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PMID:Suppression of melanoma cell motility factor receptor expression by retinoic acid. 132 86

alpha-MSH was found to decrease the recently characterized dopachrome tautomerase activity in cultures of B16/F10 mouse melanoma cells. Other stimulating agents of melanogenesis, like dibutyryl cyclic AMP, 3-isobutyl-1-methylxanthine, theophylline, retinol, and retinoic acid, caused the same effect. The grade of inhibition depended on the nature of the agent and the time of exposure. In all cases, both melanin production and tyrosinase activity were activated by these treatments, although the grade of tyrosine hydroxylase and dopa oxidase stimulation was different. Moreover, no correlation among the intensities of dopachrome tautomerase inhibition and tyrosinase activation by the tested agents could be obtained. The significance of these results in the regulation of mammalian melanogenesis is discussed.
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PMID:Alpha-MSH and other melanogenic activators mediate opposite effects on tyrosinase and dopachrome tautomerase in B16/F10 mouse melanoma cells. 132 99

Experimental efforts to identify characteristic features of metastatic subpopulations have led to the selection of strains of specialized cells with high and low metastatic potential in the hope that by studying their biochemical and biophysical properties we might start to clarify how tumour cells metastasize. We report data on the phospholipid composition of three variants of murine melanoma B16: F1, with low metastatic potential; F10, highly metastatic when injected i.v.; and BL6, highly metastatic, spontaneous metastases developing from a primary s.c. tumour. Cells were studied at different stages of growth: subconfluent cultures (40-70 x 10(3) cells/cm2) or dense cultures (140-170 x 10(3) cells/cm2). Total phospholipid content decreased as cell density increased in all variants; these changes can probably be related to the reduction in cell volume with increasing cell numbers in the well. As a consequence of this reduction, the amounts of individual phospholipids also decreased in dense cultures. Phosphatidylinositol behaved differently in the highly metastatic variants. In the F1 strain it was three times lower than would be expected from the total phospholipid reduction, while in F10 and BL6 levels increased when cell density increased. Differences in phosphatidylinositol level were also found between variants within each density, suggesting that phosphoinositide synthesis may be related to the metastatic potential of the variants. Incorporation of ([3H] myo)-inositol incorporation into phospholipids over a period of 4 h was greater in F1 cells than in F10 and BL6 at both cell densities.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res 1992 Nov
PMID:Phospholipid composition, phosphoinositide metabolism and metastatic capacity in murine melanoma B16 variants at different stages of growth. 133 2

Levels of glutathione peroxidase (GSH-PX), glutathione-S-transferase (GST), gamma-glutamyl transpeptidase (gamma GTP) and glutathione reductase (GR) activities in the B16-F10 metastatic melanoma cell line are higher than those in non-metastatic B-16 murine melanoma cells. An inverse relationship was observed between the level of reduced glutathione (GSH) and metastatic capacity. Interferon (IFN), an antitumour and antimetastic agent, reduced the experimental metastatic capacity of B16-F10 cells while increasing the intracellular GSH content. This was associated with a fall in activity of GSH-metabolizing enzymes. These results suggest a correlation of intracellular GSH and its metabolizing enzymes with malignant transformation.
Melanoma Res 1992 Dec
PMID:Intracellular glutathione and its metabolizing enzyme activities in a metastatic variant melanoma cell line. 136 79

We studied the role of the fibrinolytic function in the invasiveness of murine melanoma B16F1 and F10 cells using a reconstituted matrix on a filter in a modified Boyden chamber. The main species of plasminogen activators (PAs) synthesized in cell lysates and released into conditioned media by these cells was found to be tissue-type PA (t-PA). The invasiveness of these cell lines was enhanced by adding plasminogen to the gel matrix. This enhancing effect of plasminogen was markedly suppressed by adding anti-t-PA IgG and plasmin inhibitors into the gel matrix, but less affected by anti-urokinase-type PA (u-PA) IgG, offering more evidence to the hypothesis that the activation of the fibrinolytic system by PAs plays an important role in the invasiveness of murine melanoma B16 cell lines, and indicating that t-PA contributed more than u-PA to the invasive potential of these cells into the pericellular matrix.
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PMID:Fibrinolysis activity promotes tumor invasiveness of B16 melanoma cell lines through a reconstituted gel matrix. 138 Sep 52

In order to investigate the metastatic potential of tumors in vivo by measuring hyaluronic acid metabolism, C57BL/6 mice with B16 melanoma variants and C3H/He mice with FM3A tumor variants were evaluated using N-[18F]fluoroacetyl-D-glucosamine (18F-GlcNFAc). The uptake of 18F-GlcNFAc was slightly higher (P less than 0.05) in B16-F10 tumors (high metastatic potential) than in B16-F1 (low metastatic potential). Analysis of metabolites showed that acid-insoluble fraction was the largest one in the liver by 60 min, whereas in the tumors, phosphates fraction was the major metabolite. Slower metabolism in tumors was suggested, and it may be one of the reasons for the difficulty of detecting the characteristics of their hyaluronic acid synthesis. 18F-GlcNFAc uptake by FM3A variants showed no significant correlation with their metastatic potential. In addition, N-acetyl-D-[1-14C]glucosamine, 2-deoxy-D-[1-14C]glucose and [6-3H]thymidine failed to demonstrate any difference between tumors' metastatic variants in vivo.
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PMID:Investigation of tumor metastatic potential with N-[18F]fluoroacetyl-D-glucosamine. 139 95

Triflavin, an Arg-Gly-Asp (RGD) containing peptide purified from Trimeresurus flavoviridis snake venom, inhibits human platelet aggregation by blocking fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this study, we show that triflavin (1-30 micrograms/mouse) inhibits B16-F10 melanoma cell-induced lung colonization in C57BL/6 mice in a dose-dependent manner. In vitro, triflavin dose-dependently inhibits adhesion of B16-F10 melanoma cells to extracellular matrices (ECMs; i.e., fibronectin, fibrinogen, vitronectin, and collagen type I). Triflavin is approximately 600-800 times more potent than GRGDS at inhibiting cell adhesion. In addition, triflavin dose-dependently inhibits B16-F10 cell-induced platelet aggregation. These results imply that the inhibitory effect of triflavin on the adhesion of tumor cells to ECMs (e.g., fibronectin, vitronectin and collagen type I) and/or tumor cell-induced platelet aggregation may be partially responsible for its antimetastatic activity in C57BL/6 mice.
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PMID:Triflavin, an Arg-Gly-Asp-containing antiplatelet peptide inhibits cell-substratum adhesion and melanoma cell-induced lung colonization. 139 25

We reported earlier that oncolysate retained in the excision wound of a local tumor inhibits growth of remote tumor in the rat. We further studied this effect on pulmonary metastasis. C57BL/6 mice were given B16 melanoma F10 cells subcutaneously into the gluteal area (Day 0) and then intravenously on Day 10. On Day 14, mice were divided into four groups. Group 1 received a sham operation and no further treatment. Tumors were excised in the remaining mice. Group 2 received tumor excision alone. Groups 3 and 4 received injections of freeze-lysed tumor cells (TC) and lysate modified (PTC) with a hapten, L-phenylalanine mustard (PhM), respectively, into excision wounds. On Day 24, metastases were assessed by determining metastatic burden. Average diameters of excised tumors in repeated experiments ranged from 8.7 to 10.9 mm. In repeat experiments, pulmonary metastatic burden increased by as much as 52 to 181% in the tumor excised group (Group 2) in comparison with those receiving sham surgery (Group 1). However, metastatic burden was always reduced in Group 3. An even greater reduction was seen in Group 4. To study the possible involvement of macrophages, the production of prostaglandin-E2 (PGE2) and cytotoxicity of macrophages in these animals were examined. It was found that tumor excision enhanced PGE2 production by macrophages and suppressed their cytotoxicity, while TC inoculation prevented both of these changes. An even greater prevention was observed with PTC inoculation. These results indicate an association among macrophage cytotoxicity, PGE2 production of macrophages, and metastasis. In order to clarify the mechanism for these reactions, we did experiments using adherent splenic macrophages from the four groups of animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of local tumor removal and retained oncolysate on lung metastasis. 140 87

A morphometric analysis was carried out on electron micrographs of cells of the F1 (low metastatic capacity) and F10 (high metastatic capacity) variant sublines of the murine B16 melanoma, both in in-vitro cultures and in lung-metastatic nodules developed after the intravenous injection of neoplastic cells in syngeneic C57 black male mice. A group of 28 morphometric parameters was derived to describe quantitatively each neoplastic cell profile. No qualitative difference was observed between the two cell lines. The quantitative expression of subcellular organelles was dissimilar in the two sublines, being consistently characterized, both in in-vitro cultured cells and in lung-metastatic colonies, by a significant decrease in the mean values of parameters related to melanosomes in the high metastatic capacity cell line (B16-F10). Moreover, in in-vitro cultured cells, indices describing heterochromatin masses and cytoplasmic membranous compartments displayed statistically significant differences between the two sublines. In this experimental system, an inverse relationship between metastatic capacity and differentiation is detected, since cells with a more aggressive metastatic behavior exhibit a decreased degree of differentiation.
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PMID:Metastatic capacity and differentiation in murine melanoma cell lines. A morphometric study. 140 7

To evaluate new cytotoxic drugs for intrathecal treatment we developed an experimental model of leptomeningeal metastasis by intracisternal injection of 10(4) B16-F10 melanoma cells in nude rats. One hour in vitro incubation with 20 micrograms/ml ACNU (area under the drug concentration-time curve = 1200 microgramsxmin/ml) induced a 4-log kill of B16 melanoma cells. A single or repeated non-toxic dose of 1 mg/kg was injected into the cisterna magna of rats inoculated with tumor (area under the drug concentration-time curve assuming an even cerebrospinal fluid distribution greater than 7000 microgramsxmin/ml). Median survival free of symptoms was 16 days (range 14-27) for controls (n = 9) and 18 days (range 17-23) for rats treated with ACNU on day 4 (n = 9). Animals treated both on day 2 and 8 (n = 8) developed symptoms on day 21 (range 13-35). Neurological symptoms and neuropathological examination in animals with increased survival indicated local suppression of tumor growth in the cisterna magna but increased spinal seeding and mass growth. From these results and the available pharmacokinetic data on ACNU it is concluded that bolus injection of ACNU--although locally effective--is not a sufficient treatment of widespread leptomeningeal metastasis. An increased therapeutic efficacy might be achieved by ventriculolumbar perfusion.
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PMID:Intrathecal ACNU treatment of B16 melanoma leptomeningeal metastasis in a new athymic rat model. 143 39


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