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

Since our aim was to isolate and identify new progression markers of human cutaneous melanoma, we applied the differential hybridization technique, in which we compared the gene expression in two subsequent stages of this progression. Tumors in nude mice arising after transplantation and serial passage in vivo of either the horizontally and early vertically growing part or the advanced vertically growing part of a primary melanoma of the same patient were used for this assay. This resulted in the isolation of a number of complementary DNA clones that were differentially expressed. Based on the marked difference in expression, one of them, designated pMW1, was chosen for further characterization and appeared to be coding for calcyclin, a cell cycle-regulated protein, belonging to a family of small calcium-binding proteins. Calcyclin expression was elevated in high-metastatic human melanoma cell lines in nude mice compared to low-metastatic ones. Immunoprecipitation of calcyclin showed that the differential expression at the RNA level is also reflected at the protein level. These findings show that expression of calcyclin is related to metastasis of human melanoma cell lines in nude mice and emphasize the role of this family of calcium-binding proteins in neoplastic progression as was reported for the mouse homologue of calcyclin and other members of the same family.
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PMID:Expression of calcyclin in human melanoma cell lines correlates with metastatic behavior in nude mice. 173 92

A previous observation of increased aqueous magnesium in eyes with senile cataract has been re-examined in a totally different material. The serum and aqueous level of calcium and magnesium from 34 patients with senile cataract were tested against comparable values from 4 patients with choroidal melanoma. In contrast to calcium, the magnesium aqueous/serum ratio was significantly higher in the cataract group. Possible explanations are suggested.
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PMID:Increased magnesium in aqueous humour from patients with senile cataract. 175 Mar 27

To examine the potential role of lipoxygenase products in the pathophysiology observed after experimental tumor implantation, we examined the generation of leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) in peritoneal macrophages. C57BL/6 mice were given subcutaneous inoculations of B16 melanoma cells, and peritoneal macrophages were isolated various days after the inoculation. Macrophages were incubated for 1 h at 37 degrees C in serum-free RPM11640 containing 10 microM calcium ionophore A23187, 10 microM exogenous arachidonic acid (AA), 5 mM cysteine hydrochloride and 1 mM reduced glutathione. LTs and HETEs were separately extracted, passed through Sep-Pak cartridges, then identified and quantitated with a HPLC system using UV absorbance. The B16 melanoma-cell-treated/untreated macrophages were found to produce substantial amounts of 15-HETE, 12-HETE and 5-HETE and LTC4 by enzymatic mechanisms. Thus, when determined under various conditions, the production of HETEs was dependent on substrate-concentration, incubation-time and cell-number. The production of LTC4 was dependent on incubation-time and cell number but not substrate-concentration, indicating utilization of endogenous AA stores. Of these products, 12-HETE and LTC4 showed a significant increase on the fourth day after the tumor cell inoculation and returned to the control level by the 11th day after the same treatment. These results suggest that in vivo tumor cell implantation may induce a transient increase of 12-HETE and LTC4 production in macrophages.
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PMID:Generation of leukotrienes and hydroxyeicosatetraenoic acids in peritoneal macrophages of tumor-bearing mice. 180 27

The importance of thioproteins, essential to the ribonucleotide reduction pathway, has been demonstrated in human primary and metastatic melanoma tissues. The thioredoxin reductase/thioredoxin and the glutathione reductase/glutathione/glutaredoxin electron transfer pathways represent alternative electron donors for ribonucleotide reductase and regulate the synthesis of deoxyribonucleotides, the substrates for DNA synthesis, in the S phase of the cell cycle. In addition to their important role in DNA synthesis and cell division, these thioproteins provide effective antioxidant defence against oxygen radicals and hydrogen peroxide. In human metastatic melanoma cells and tissues the thioredoxin reductase/thioredoxin system is located both in the cell cytosol and on plasma membranes and is under allosteric regulation by calcium. As a consequence, calcium plays an important role in determining the intracellular redox status, cell division and differentiation. Recently, the intracellular redox conditions have been shown to be important in the reaction of alkylating anti-tumour drugs such as the chloroethylnitrosoureas. In addition to previously established mechanisms, these highly reactive drugs inhibit thioredoxin reductase, glutathione reductase and ribonucleotide reductase by chloroethylation of their respective thiolate active sites. Incorporation of the 14C chloroethyl group in drug sensitive and resistant human metastatic melanoma cell lines depends on the redox status, with resistant cells being more oxic than sensitive cells. Thioredoxin reductase is 500-fold more sensitive than glutathione reductase to the newly developed nitrosourea, Fotemustine (diethyl-1-[3,2 chloroethyl]-3-nitrosoureido ethyl phosphonate). It has been shown that melanomas which respond to Fotemustine therapy contain more thioredoxin reductase whereas resistant metastases yielded the opposite result.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res
PMID:New aspects in the pathophysiology of cutaneous melanoma: a review of the role of thioproteins and the effect of nitrosoureas. 184 12

We investigated the in vitro mechanism of platelet aggregation induced by HMV-I human melanoma cells. HMV-I cells, in the absence of exogenous plasma proteins, induced platelet aggregation, followed by the release reaction. Heparin at an anticoagulant concentration had no effect on the aggregation. Calcium ion was essential for this tumor cell-platelet interaction and could not be replaced by magnesium. Among the adhesive proteins containing RGD sequences that have been reported to enhance experimental metastasis, fibrinogen and thrombospondin significantly enhanced the aggregation induced by HMV-I cells, fibronectin and von Willebrand factor inhibited it, and vitronectin had no effect. To identify the platelet-aggregating factor(s) of the tumor cells, we have developed a monoclonal antibody against HMV-I cells that can inhibit HMV-I cell-induced platelet aggregation. Immunoprecipitation analysis revealed that this antibody recognized an Mr 71,000 membrane protein. These results suggest that the association between the tumor cells and platelets is mediated by the Mr 71,000 membrane protein recognized by this monoclonal antibody.
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PMID:Characterization of platelet aggregation induced by the human melanoma cell line HMV-I: roles of heparin, plasma adhesive proteins, and tumor cell membrane proteins. 184 62

Phospholipase C was purified from human melanoma grown as solid tumors in nude mice. The specific activity of the pure enzyme was approx. 100 mumol/min per mg; its apparent molecular mass was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis to be 150 kDa. The enzyme required calcium for activity and was activated by deoxycholate in the presence of the substrate phosphatidylinositol. The melanoma phospholipase C has a distinctly different substrate preference than those identified from normal tissues; it prefers phosphatidylinositol to phosphatidylinositol bisphosphate. The tumor enzyme was approx. 4-5-fold more active using phosphatidylinositol than phosphatidylinositol bisphosphate as the substrate.
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PMID:Phospholipase C from human melanoma: purification and characterization of a phosphatidylinositol-selective enzyme. 184 29

SC1, an integral membrane glycoprotein of 100 kd, is uniquely and transiently expressed on spinal cord motoneurons early in development and appears in peripheral neurons and several other tissues during development. SC1 has been purified by immunoaffinity techniques, and SC1 cDNA clones have been obtained by screening an E4 chick embryo phage expression library with a rabbit polyclonal antibody produced against purified SC1. The deduced protein sequence of 588 amino acids consists of a signal peptide, five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail. The sequence is most similar to MUC18, reported as a tumor progression marker in human melanoma. Transfection of SC1 cDNA into mammalian cells leads to cell surface expression of SC1 antigen and a subsequent increase in cell-cell adhesion. SC1 molecules bind to each other via a homophilic adhesion mechanism, independently of calcium or magnesium ions. SC1 may have a role in lateral motor column formation or neurite growth or fasciculation.
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PMID:Molecular cloning and expression of a novel adhesion molecule, SC1. 193 Oct 49

Plasma membrane-associated thioredoxin reductase activities have been determined on primary melanoma tissues and their surrounding skin in 29 patients. Compared to patient's normal skin, enzyme activities in melanoma were higher in some patients (n = 24) and lower in others (n = 5). Those melanomas with high TR activities yielded low activities in the adjacent epidermis, reaching normal activity 3 to 5 cm away from each primary site (n = 4). Tumors with low activities showed higher than normal activities on the immediate surrounding skin (i.e., 1 cm away from the tumor) compared to the normal skin (n = 3). Earlier it was shown that in both keratinocytes and melanoma cells, calcium regulates thioredoxin reductase activity by an allosteric mechanism. The differences in TR activities within the high and low groups may be caused by a calcium flux between the primary tumor and the surrounding epidermis, and vice versa. A comparison of TR activities to tumor invasiveness (Breslow level) in 28 primary melanomas showed a significant correlation using regression analysis (p = 0.031). A 4-fold difference in TR activity corresponds to a one-unit change in Breslow determination. These preliminary results suggest that TR activity may be another useful and sensitive assay for melanoma spread.
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PMID:Thioredoxin reductase activity at the surface of human primary cutaneous melanomas and their surrounding skin. 201 54

Long wave ultraviolet radiation (UVA) has been shown to play an important role in the overall response of skin to solar radiation, including sunburn, tanning, premature aging, and non-melanoma skin cancer. UVA induction of inflammation in human skin is thought to be mediated by membrane lipid derived products. In order to investigate the mechanism of this response we examined the effect of UVA on phospholipid metabolism of human epidermal keratinocytes in culture. Keratinocytes were grown in serum free low calcium medium. The cells were prelabeled with [3H] arachidonic acid or [3H] choline and irradiated with UVA (Honle 2002-Hg vapor lamp). Identification and quantitation of specific membrane phospholipid-derived components was achieved using high-performance liquid chromatography, paper chromatography, and radioimmunoassay. UVA resulted in a linear dose dependent release of [3H] arachidonic acid into medium between 1 and 20 joule/cm2. This response was inhibited in an oxygen-reduced environment. The radiolabel released was predominantly free arachidonate and cyclooxygenase metabolites. Cyclooxygenase metabolites prostaglandin E2 and prostacyclin derivative, 6-keto-prostaglandin F1a, were stimulated following UVA irradiation, but the lipoxygenase metabolite, leukotriene B was not detected. Maximal release was measured immediately after irradiation and changed little over 24 h post-irradiation. UVA stimulated an increase of [3H] choline metabolites glycerophosphorylcholine and phosphorylcholine in media extracts suggesting UVA activation of phospholipase C and phospholipase A2 or diacylglyceride lipase.
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PMID:Long-wave ultraviolet light induces phospholipase activation in cultured human epidermal keratinocytes. 211 82

A positive association between agonist-stimulated cyclic AMP production in vitro and both experimentally induced (B16 melanoma) and spontaneous (fibrosarcoma) metastases were found. Five B16 melanoma cell lines producing varying degrees of lung colonization following intravenous injection and three hamster fibrosarcoma cell lines producing a varying number of metastases in lungs and regional lymph nodes after removal of the primary tumour were studied. Agonist-stimulated (forskolin and melanocyte-stimulating hormone), but not basal cyclic AMP accumulation, increased with increasing metastatic potential. This relationship did not extend to other intracellular signalling systems as determined by investigation of basal or foetal-calf stimulated phosphatidylinositol hydrolysis for either tumour type. Intracellular free calcium was also similar in B16 melanoma cell lines of varying metastatic potential.
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PMID:A positive association between agonist-induced cyclic AMP production in vitro and metastatic potential in murine B16 melanoma and hamster fibrosarcoma. 216 81


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