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)

Extracts of conditioned medium (CM) from Hs0294 human malignant melanoma cells stimulate [3H]thymidine incorporation and an increase in cell number in serum-depleted Hs0294 cells. This activity is acid and heat stable, nonproteolytic, protease sensitive, contains disulfide bonds and elutes broadly from a Bio-Gel P-30 column with an approximate molecular weight range of 6,000 to 25,000. Hs0294 CM also stimulates [3H]thymidine incorporation in nonmalignant human nevus cells and normal rat kidney fibroblast cells but not in human fibroblasts. There was only limited competition with 125I-epidermal growth factor in binding assays. Hs0294 CM extracts stimulate anchorage-independent growth in normal rat kidney fibroblast cells in soft agar but not in Hs0294 cells, nevus cells, or human fibroblasts. This second activity elutes from the Bio-Gel P-30 column in two positions with apparent molecular weights of 27,000 and 11,000.
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PMID:Extraction of a melanoma growth-stimulatory activity from culture medium conditioned by the Hs0294 human melanoma cell line. 660 Sep 64

In previous studies, cultured melanoma cells were shown to have a suppressive influence on the induction of cytotoxic T cells. Our investigation of the mechanism of these effects revealed that supernatants from certain cultures of melanoma cells contained inhibitory activity against the production of interleukin 2 (IL 2) from phytohemagglutinin (PHA)-stimulated cultures of lymphocytes. These supernatants did not inhibit interleukin 1 production, and also did not inhibit the mitogenic activity of performed IL 2 on IL 2-dependent target cells. Production of the inhibitory activity could be reduced by inhibitors of protein synthesis, but this activity was not inhibited by digestion with the proteolytic enzymes trypsin or pronase. Gel filtration analysis of tumor supernatants revealed that the majority of the inhibitory activity was detected in fractions of approximately 44 and 7 Kd. The addition of supernatants with inhibitory activity to PHA-stimulated cultures of lymphocytes was associated with reduced transition of cells from G1 to S phase of cell division, which could be reversed by the addition of IL 2. Preliminary studies suggest that the release of the factor(s) from melanoma cells may be related to rapid progression of tumor growth in patients, and therefore may be of prognostic significance in tumor host relationships.
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PMID:Inhibition of interleukin 2 production by factors released from tumor cells. 660 93

Two major findings are reported in the present studies: (a) Long-term cultivation, followed by cloning, of a human malignant melanoma HMMC-ShA cell line gave melanotic and amelanotic cell variants. During in vitro proliferation, the melanotic melanoma (HMMC-ShAE+) cells released carcinoembryonic antigen (CEA) and an inhibitor of phytohaemagglutinin-induced lymphocyte stimulation. Gel filtration patterns of CEA on Sephadex-G200 varied from one culture condition to another. Glycosylation-deficient CEA obtained from cells harvested from media supplemented with non-toxic levels of tunicamycin showed lower molecular weight and delayed filtration through Sephadex-G200. (b) Human melanotic melanoma (HMMC-ShAE+) differed from amelanotic melanoma (HMMC-ShA-) and glycosylation-deficient cells in the amount of CEA and in the suppression of lymphocyte response activity which they shed into the medium and as well as in oncogenicity in athymic nu/nu BALB/c mice.
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PMID:Carcinoembryonic antigen from human malignant melanoma cells. I. Production and shedding characteristics. 667 24

A branched polypeptide drug carrier, with a poly(L-lysine) backbone, has been labelled with 111In and its biodistribution imaged in mice with transplanted B16 melanoma. Levels of tracer in tumours were not great enough for tumours to be discerned on gamma-camera images, and this was confirmed by subsequent dissection analysis. Tumour levels of 111In from labelled polymer were about 3% of the dose g-1 two days after injection. Similar levels of tracer were found in tumour tissue of mice injected with mouse immunoglobulin or serum albumin labelled with 111In by DTPA chelation, or injected with free 111In-chloride to label serum transferrin. There was rapid excretion of a sub-component of the 111In-labelled polymer visible in the images. Gel permeation chromatography suggested that the polymer was heterogeneous, some components having Stoke's radii below that allowing renal clearance. Gel permeation chromatography was used to separate labelled polymer into fractions having high, intermediate and low renal clearance. The low-excretion fraction showed a two-fold increase in tumour levels, compared with native polymer, although as this fraction showed greater survival in the blood and body as a whole, discrimination between tumour and normal tissue was not increased.
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PMID:Scintigraphic determination of the biodistribution of an 111In-labelled poly(L-lysine) backbone branched polypeptide drug carrier in tumour-bearing mice. 763 52

By using p-nitrophenyl-beta-D-glucopyranoside as substrate, beta-glucosidase activity was observed in fetal bovine serum (FBS). This activity could be inhibited by heat inactivation of the serum. Gel chromatography of FBS indicated the presence of beta-glucosidase activity with an apparent molecular mass of 29 kDa. In McCoy's 5A medium supplemented with non-heat inactivated FBS, the diglucoside hypoxoside ([E]-1,5-bis[4'beta-D-glucopyranosyloxy-3'-hydroxyphenyl]pent-4-en - 1-yne) showed cytotoxicity toward B16-F10-BL-6 mouse melanoma cells. In incubations where the media were supplemented with FBS previously heat inactivated at 56 degrees C for 1 h or more, no cytotoxicity was observed in the presence of hypoxoside. The aglucone of hypoxoside, rooperol ([E]-1,5-bis[3',4'-dihydroxyphenyl]pent-4-en-1-yne), showed cytotoxicity regardless of whether the serum was heat inactivated or not. The kinetics of the heat inactivation of the beta-glucosidase activity in FBS coincided with the loss of apparent cytotoxicity of hypoxoside. High performance liquid chromatography analysis showed that rooperol could be generated by incubation of hypoxoside in non-heat inactivated FBS, but that this ability was lost in serum that was heat inactivated for 1 h or longer. Newborn bovine serum did not contain any beta-glucosidase activity whereas it was found in three different commercial sources of FBS. This observation is of practical importance because conventional heat inactivation of FBS at 56 degrees C for 30 min was not sufficient to inactivate the beta-glucosidase activity completely.
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PMID:beta-Glucosidase activity in fetal bovine serum renders the plant glucoside, hypoxoside, cytotoxic toward B16-F10-BL-6 mouse melanoma cells. 801 53

The highly metastatic B16a melanoma has been shown to express higher levels of cathepsin B (CB) mRNA when compared to the less metastatic variants, B16-F1 and B16-F10, and with normal mouse tissues. This increased expression is now shown to be due to increased gene transcription by nuclear run-off assays and measurements of mRNA stability. Transient expression assays, using promoter fragments from the mouse and human CB genes, demonstrated that both promoters were more active in B16a than in the less metastatic melanomas, B16-F1 and B16-F10. The differential gene expression did not depend on the presence of multiple Sp1 sites in both promoters. A Gel shift assay revealed a specific CB promoter binding protein whose levels are correlated with CB expression and the metastatic potential of the three B16 melanoma variants. These results indicate that the increased expression of CB in the B16a melanoma is due to a specific increase in the amount or activity of a transcriptional activator of the CB gene. The ability of the human CB promoter to activate gene expression in B16a melanoma cells suggests similarities in the regulation of CB expression in tumors from humans and mice.
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PMID:Transcriptional regulation of cathepsin B expression in B16 melanomas of varying metastatic potential. 803 44

In a phase 1 study of recombinant interleukin-6 (rIL-6) in patients with advanced solid tumors (n = 15), we discovered that the endogenous IL-6 levels, in pretreatment plasma or serum samples, were distributed into two groups. One set of patients (designated "type 1"; n = 9) was characterized by low plasma IL-6 levels (48 to 1,700 pg/mL) as measured using enzyme-linked immunosorbent assays (ELISA) for IL-6. In the second set of patients (designated "type 2"; n = 6), IL-6 ELISAs showed high levels of plasma IL-6 (50 to 600 ng/mL). Neither group had detectable B9 hybridoma cell growth factor activity associated with the IL-6 in their pretreatment plasma or serum. Plasma C-reactive protein (CRP) levels were markedly elevated in type II patients suggesting that the circulating IL-6 was biologically active in vivo. In both groups of patients there was a small but significant increase in B9 activity in the plasma within three hours after rIL-6 administration (n = 5). Gel filtration profiles showed that circulating IL-6 in type 1 patients, 15 to 120 minutes after rIL-6 administration was of approximate mass 20 to 40 kD, whereas in type 2 patients, the IL-6 before and after exogenous rIL-6 administration was indistinguishable and was of an approximate mass of 200 kD. IL-6 immunoaffinity purification of the 200 kD complexes showed these to contain multiple isoforms of IL-6 (14 to 31 kD) and the soluble IL-6 receptor (sIL-6R; 50 to 55 kD). A distinguishing clinical history was that all of the type 2 patients had been actively immunized with an anti-idiotypic monoclonal antibody (MoAb) (MK2-23) 3 to 12 months before initiation of this study for advanced melanoma. An analysis of the plasma IL-6 content in other melanoma patients (n = 16) during antiidiotypic MoAb immunization indicated that marked (up to 600 ng/mL) and sustained (several months) elevations of circulating "chaperoned" IL-6 were induced by active immunization regimens.
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PMID:Sustained high levels of circulating chaperoned interleukin-6 after active specific cancer immunotherapy. 808 Sep 95

Tumor progression is frequently associated with changes in responsiveness of tumor cells to paracrine growth factors. A potential major source of such paracrine factors in solid tumors are endothelial cells since this type of cell can constitute a sizeable fraction of the cellular composition of solid tumors. As an initial step to examining the possible effects of endothelial cell-associated growth factors on tumor cell growth, a panel of human melanoma cell lines representative of different stages of tumor progression was employed for studies utilizing endothelial cell-derived growth modulators. Macrovascular or microvascular human endothelial cells from umbilical vein or from skin, respectively, inhibited melanoma cell growth in direct coculture experiments. The potency of this inhibitory effect diminished as a function of melanoma progression. Conditioned media from endothelial cell cultures mimicked the effect of the cell coculture experiments, suggesting the involvement of soluble growth factor(s). Approximately 50-75% of the conditioned media inhibitory effect was abrogated by addition of the neutralizing antibody to interleukin-6 (IL-6). Gel filtration chromatography revealed the presence of additional inhibitors in endothelial cell conditioned medium. Two peaks of activity were detected with apparent molecular weights of approximately 100-150 Kd and 20-30 Kd, the latter containing IL-6 activity. Whereas early-stage radial growth phase (RGP) primary tumor-derived melanoma cells were sensitive to at least three different endothelial products of high or low molecular weight (including IL-6), melanoma cells from more advanced metastatic lesions were resistant to the latter activities, and retained only partial sensitivity to the high molecular weight inhibitor. More advanced vertical growth phase (VGP) primary melanoma cell lines expressed intermediate inhibition-sensitive phenotypes. Thus human melanoma development appears to be associated with progressive loss of sensitivity to the growth inhibitory effects of IL-6 and other factors produced by endothelial cells. This is likely to be a result of a selection process when tumor cells are confronted with adjacent vasculature during the progress of tumor angiogenesis.
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PMID:Progressive loss of sensitivity to endothelium-derived growth inhibitors expressed by human melanoma cells during disease progression. 816 65

In herpes simplex virus-infected (HSV) cells, the antiviral nucleoside analogue 5-n-propyl-2'-deoxyuridine (PdU) may, under certain circumstances, induce a pattern of interference with late steps in formation of N-linked glycans, resulting in increased availability of viral glycoproteins for neutralizing antibodies. The PdU-induced changes in N-linked glycans, released by pronase digestion of the HSV-specified glycoprotein gC-1, were investigated by using lectin affinity chromatography and Bio-Gel P6 gel filtration of glycans, radiolabelled with [3H]galactose or [3H]glucosamine. PdU-treatment of HSV-infected cells totally inhibited addition of sialic acid and reduced the amount of galactose incorporated into N-linked glycans by 70%. In addition, the PDU-treatment caused a decrease in oligosaccharides with affinity for Phaseoulus vulgaris leuco-agglutinin and erythro-agglutinin, and an increase in Lens culinaris lectin (LCA)-binding oligosaccharides, suggesting a PdU-induced shift from multi-branched to moderately branched structures. This shift was also found in HSV-infected B16 mouse melanoma cells, where the large content of multi-branched oligosaccharides contributes to the metastatic potential. The LCA-binding glycans from PdU-treated cells were smaller and contained less galactose units than corresponding structures from untreated cells. In a cell-free system, PdU 5'-monophosphate inhibited the translocation of UDP-GlcNAc, and, to a smaller extent, also the translocation of UDP-galactose into Golgi vesicles, suggesting that nucleotide sugar translocation is one important target for the PdU-induced interference with glycosylation in HSV-infected cells.
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PMID:5-Propyl-2-deoxyuridine induced interference with glycosylation in herpes simplex virus infected cells. Nature of PdU-induced modifications of N-linked glycans. 838 38

High constitutive expression of the c-myc oncogene in human melanoma leads to downregulation of expression of HLA Class I genes. The genes at the HLA-B locus are preferentially affected. To investigate the mechanism of downregulation, the activity of the main HLA Class I enhancer, enhancer A-region I, was compared in a panel of c-myc transfectants with increasing myc expression. Gel retardation experiments demonstrated in all tested cell lines binding of the transcription factors KBF1 and NF-kappa B to the enhancer. However, no correlation between the levels of HLA Class I expression and binding to the enhancer could be established. Strikingly, the cell line with the highest c-myc expression showed more binding of KBF1 and NF-kappa B than the parental cell line. By using CAT reporter plasmids in transient transfection assays we investigated the in vivo function of enhancer A-region I in the c-myc transfectant panel. Again, c-myc expression had no effect at all on the activity of enhancer A. This study shows that HLA Class I expression is regulated by the c-myc oncogene at the level of transcription, but that the main HLA Class I enhancer is not involved in this process.
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PMID:Downregulation of HLA class I expression by c-myc in human melanoma is independent of enhancer A. 846 2


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