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)

Phorbol ester (12-O-tetradecanoyl-phorbol 13-acetate) stimulates the secretion of tissue-type plasminogen activator by the melanoma cell line, Bowes. This effect is associated with increased levels of mRNAs for both tissue-type plasminogen activator and a 48 kDa-protein. Labelling of melanoma cells with L-[35S]methionine allowed to identify an intracellular protein which, by 3 criteria, was identical with the in vitro translation product of the 48kDa-protein mRNA: a Mr of 48,000 on electrophoresis in the presence of sodium dodecyl sulphate; inducibility by phorbol ester and failure of reducing agents to affect electrophoretic mobility. As detectable by L-[35S]methionine labelling, the protein was mainly localized in the cytosol. In vitro phosphorylation reactions, carried out on subcellular fractions revealed a membrane-associated protein which also had the three characteristics of the aforementioned 48 kDa-protein. Phosphorylation did not require Ca2+-ions. Addition of phorbol ester to the reaction mixtures increased the phosphorylation. Reconstitution experiments between membrane and cytosol fractions of phorbol ester-treated and untreated cells showed that the 48kDa protein occurs in a cytosolic, unphosphorylated and a membrane-bound, phosphorylated form and that the former is converted to the latter by a phorbol ester activated, membrane-associated protein kinase.
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PMID:Phorbol ester stimulates the synthesis and phosphorylation of a 48 kDa-intracellular protein in plasminogen activator secreting melanoma cells. 308 56

Challenge of human or murine melanoma cells with sodium arsenite, heavy metals (Zn2+, Cu2+ and Cd2+), or thiol-reactive agents (p-chloromercuribenzoate and iodoacetamide) induced the synthesis of four stress proteins with molecular masses of 100, 90, 72 (a doublet), and 32 (human) or 34 (murine) kDa. Enhanced expression of the 32- and 34-kDa polypeptides (p32 and p34) preceded or paralleled the synthesis of the other stress proteins. Hyperthermia, the calcium ionophore A23187, and amino acid analogs (L-azetidine-2-carboxylic acid and L-canavanine) induced the formation of the major stress proteins, but failed to increase synthesis of p32 and p34. Characterization of the dose and time dependence of p32 and p34 synthesis in human (A375) and murine (B16-F10) melanoma cells, respectively, indicated that these proteins were subject to similar regulatory mechanisms. Electrophoretic analysis of stressed cells pulsed with different metabolic precursors revealed that p32 and p34 were radiolabeled with [35S]methionine or 3H-amino acids but not by [3H]mannose or [35S]cysteine. Polyclonal antibodies raised against human p32 cross-reacted with murine p34. These data suggest that p32 and p34 are closely regulated human and murine gene products, respectively, whose synthesis can be modulated by thiol-reactive reagents. Induction of p32 and p34 by these agents, but not by heat shock, suggests that these proteins are a subset of stress-inducible gene products.
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PMID:Induction of 32- and 34-kDa stress proteins by sodium arsenite, heavy metals, and thiol-reactive agents. 309 79

Administration of calcium disodium edetate (EDTA) substantially increased the tumor:muscle ratios of nude mice injected with 111In labeled monoclonal antibody 9.2.27. This effect was apparent 3 days to 7 days after antibody injection of mice bearing the BRO human melanoma, but not earlier. The tumor:muscle ratios decreased during this time for animals not receiving chelator. Contemporaneously, EDTA treated mice lost whole body radioactivity more rapidly than did their untreated counterparts, suggesting that 111In which had dissociated from the antibody-DTPA-radiometal complex was chelated and excreted. These results suggest that effective chelator treatment might improve tumor localization of radioactivity after injection of 111In labeled antibodies.
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PMID:Improved tumor localization of 111In labeled monoclonal antibody with chelator administration to host nude mice. 310 43

Homologous human macrophage hybridoma cell lines were obtained by somatic cell fusion between peripheral blood monocyte-derived macrophages and a subclone of the myelomonocytic cell line, U937-F9. The hybridoma cell lines grown in vitro for more than a year were confirmed by manifestations of phagocytosis, adherence, nonspecific esterase, acid phosphatase, chromosome numbers and other cell surface antigens. Cell surface antigens on hybridomas were detected by flow cytometry analysis with monoclonal antibodies. With interclonal differences, a typical phenotype of hybridoma cells was CDw14+, OKM5+, Mac-1+ (equivalent to OKM1 and Mol), OKT9+, HLA-DR- and CD20+. After stimulation with lipopolysaccharide and calcium ionophore A23187, culture supernatants of clones c18A and c29A showed cytotoxic activity against human melanoma A375 Met-Mix and other cell lines which were resistant to the tumor necrosis factor, lymphotoxin and interleukin 1. This cytotoxic factor was found to be distinct from the tumor necrosis factor, lymphotoxin and interleukin 1 using the anti-tumor necrosis factor, anti-lymphotoxin and anti-interleukin 1 antisera.
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PMID:Homologous human macrophage hybridomas that produce a novel cytotoxic factor in their culture supernatants. 328 4

Five out of 6 cell lines derived from metastatic melanoma lesions grew in a chemically defined base medium consisting of a mixture of calcium-supplemented MCDB 153 and L 15 media in the absence of any polypeptide growth factors. In contrast, under these conditions no growth was seen in any of 5 primary melanoma cell lines tested, including 2 cell lines from patients whose metastatic cells proliferated well in base medium. Growth stimulation of all 11 melanoma cell lines by epidermal growth factor (EGF), transferrin, insulin, and insulin-like growth factor (IGF)-1 alone and in various combinations was studied. Insulin represented the strongest single growth factor for primary and metastatic melanoma cell lines. The metastatic cell lines remained growth-responsive to EGF, insulin and transferrin and responded more vigorously to these exogenously provided mitogens than the primary cell lines. No synergistic or additive growth effects of insulin, transferrin, or EGF for primary and metastatic cell lines were observed. Cross-linking studies with 125I-IGF-1 demonstrate surface expression of the type-I IGF receptor on melanoma cells. Growth stimulation by insulin and IGF-1 was inhibited by adding to the culture medium a monoclonal antibody to the type-I IGF receptor. Our studies indicate that IGF-1 and insulin are major growth factors for melanoma cells and act via the type-I IGF receptor.
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PMID:Metastatic but not primary melanoma cell lines grow in vitro independently of exogenous growth factors. 331 51

Eyes of cutaneous melanoma-bearing miniature Sinclair swine were examined by light and electron microscopy during growth and maturation of animals. The histology of ocular depigmentation, which occurs during melanoma arrest and skin depigmentation, was studied in eyes of animals that had successful and unsuccessful tumor regression. In 12 animals one eye was removed at an early stage and the second eye at a later stage of disease or maturation. The histologic and clinical course of the ocular changes was correlated with changes in the cutaneous tumors. Animals showing rapid cutaneous tumor regression developed acute uveitis that was characterized by an influx of mononuclear cells into the stroma of the ciliary body; later this spread to the iris and choroid. In late stages the cornea sometimes developed a band of calcium precipitates beneath the basal epithelial cells (band keratopathy). Uveal melanocytes developed watery cytoplasm typical of cells with ruptured plasma membranes. Released melanin granules were taken up initially into the lysosomal compartment of mononuclear cells having the various morphologic features of lymphocytes and monocytes; later, melanin also appeared in fibrocyte lysosomes. The relationship of these processes to various cell-mediated immunity phenomena is being studied.
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PMID:Ocular pathology in melanomatous Sinclair miniature swine. 335 45

External ATP causes a marked increase in the passive permeability to phosphorylated metabolites in several types of transformed cells in alkaline medium containing low concentrations of Ca2+, but not in untransformed cells. Such increased membrane permeability with external ATP was also observed in B16 melanoma cells at pH 7.4-7.5 in both Tris-buffered saline and a growth medium containing 10% calf serum and divalent ions at normal concentrations, although a higher concentration of ATP was required. The permeability change in the growth medium was significantly enhanced by calmodulin-interacting drugs, such as trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) and chlorpromazine (CPZ). As expected, prolonged exposure of the cells to ATP in the serum-containing medium led to cell lysis. This ATP-dependent cell lysis was observed only in several transformed cell lines, and not in untransformed mouse fibroblasts. These results indicate that the effect of ATP on the membrane permeability in transformed cells is elicited under the physiological conditions and this would be useful in some limited way for cancer chemotherapy management.
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PMID:External ATP-induced passive permeability change and cell lysis of cultured transformed cells: action in serum-containing growth media. 338 48

A strong correlation was found between the basal levels of membrane-bound protein kinase C and the ability of B16 melanoma cell sublines (F10, F1, and BL6) to metastasize to the lung after intravenous injection. By treating with tumor-promoting phorbol esters for 1 hr, the low-metastasizing F1 cells exhibited both translocation of protein kinase C from cytosol to plasma membrane and an increase in metastasis to a level comparable to the (untreated) highly metastatic subline F10. Prolonged treatment of melanoma sublines with phorbol 12-myristate 13-acetate for 24 hr resulted in both inactivation of protein kinase C activity and loss of their metastasizing capabilities. Under conditions that induced only the activation of protein kinase C but not its membrane association, no increase in metastasis occurred, suggesting that activation of protein kinase C alone is insufficient to promote metastasis and that its membrane association is also necessary. Exposure of B16 melanoma sublines to phorbol esters for 1 hr had (i) no effect on the growth and morphology of these cells in vivo and in vitro and (ii) a short-term effect (approximately equal to 5 hr) on membrane association of protein kinase C. Nonetheless, in this period, the membrane-bound protein kinase C, probably by influencing cell-surface and cell-attachment properties, increased the retention of circulating melanoma cells in the lung, which eventually led to an increased number of metastatic nodules. The membrane-bound protein kinase C activity also correlated with metastatic ability in rapidly growing cells, growth-arrested cells, and cells growing in a low-Ca2+ medium. The results strongly suggest that the membrane-bound protein kinase C influences hematogenous metastasis of tumor cells and show that tumor promoters like phorbol esters have an additional role in promoting hematogenous spread of cancer in the body.
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PMID:Tumor promoter-induced membrane-bound protein kinase C regulates hematogenous metastasis. 342 45

A 70-kDa channel-forming protein has recently been isolated from human large granular lymphocytes maintained in interleukin-2-dependent culture. The protein was shown to be immunochemically related to the ninth component of complement (C9) and was therefore designated C9-related protein (C9RP). Using the procedure that was developed for the isolation of C9RP from large granular lymphocytes--i.e., affinity chromatography employing anti-human C9 linked to Sepharose, a cytolytic protein has now been isolated from OKT3-activated human peripheral blood mononuclear cells. Nineteen to 40 micrograms of active protein was obtained from 1 X 10(9) human peripheral blood mononuclear cells after the cells were cultured for 3 days with OKT3 (monoclonal antibody to cell surface antigen T3). During this period, a marked increment occurred in the amount of the cytotoxic protein contained per cell, indicating that OKT3 induced de novo synthesis of the protein. By NaDodSO4/PAGE the molecular mass was determined to be 70 kDa. By ELISA the isolated protein and C9RP of large granular lymphocytes reacted to the same extent with anti-C9RP. Using K-562 or M21 human melanoma cells as targets, the cytotoxic activity of the isolated protein, in the presence of 5 mM Ca2+, was comparable to that of C9RP. The same cytolytic protein was isolated from peripheral blood mononuclear cells that were depleted of CD16+ cells prior to OKT3 activation and that consisted primarily of CD4+ and CD8+ T lymphocytes. These results suggest that the cytolytic protein of OKT3-activated cytotoxic T lymphocytes is identical with C9RP of interleukin-2-stimulated large granular lymphocytes.
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PMID:The cytolytic protein of human lymphocytes related to the ninth component (C9) of human complement: isolation from anti-CD3-activated peripheral blood mononuclear cells. 349 51

Flunarizine, a calcium antagonist commonly employed in therapy for vascular diseases, enhances the in vitro and in vivo antitumor activity of vincristine on B16 melanoma cells. In the presence of flunarizine higher intracellular levels of vincristine were observed in vitro and for a longer time. B16 melanoma bearing mice treated with both the drugs presented a median survival time that was significantly longer than that of the controls. The possible mechanism of the enhancement is herein discussed.
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PMID:In vitro and in vivo enhancement of vincristine antitumor activity on B16 melanoma cells by calcium antagonist flunarizine. 356 23


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