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

A melanoma proteoglycan model system has been used to examine the role of core protein asparagine-linked (N-linked) oligosaccharides in the transport and assembly of proteoglycan molecules. The use of agents which block discrete steps in the trimming and processing of core oligosaccharides (castanospermine, 1-deoxynojirimycin, N-methyldeoxynojirimycin, 1-deoxymannojirimycin, and swainsonine) demonstrates that removal of glucose residues from the N-linked oligosaccharides is required for the cell surface expression of a melanoma proteoglycan core protein and for the conversion of the core protein to a chondroitin sulfate proteoglycan. However, complete maturation of the oligosaccharides to a "complex" form is not required for these events. Treatment of M21 human melanoma cells with the glucosidase inhibitors castanospermine, 1-deoxynojirimycin, or N-methyldeoxynojirimycin results in a dose-dependent inhibition of glycosaminoglycan (GAG) addition to the melanoma antigen recognized by monoclonal antibody 9.2.27. In contrast, treatment with the mannosidase inhibitors 1-deoxymannojirimycin and swainsonine does not effect GAG addition. Identical results are obtained when the major histocompatibility complex class II antigen gamma chain proteoglycan is examined in inhibitor-treated melanoma and B-lymphoblastoid cells. These data, in conjunction with the known effects of the glucosidase and mannosidase inhibitors on the transport and secretion of other glycoproteins support the hypothesis that the addition, trimming, and processing of N-linked oligosaccharides is involved in the transport of certain proteoglycan core proteins to the site of GAG addition and to the cell surface.
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PMID:Post-translational addition of chondroitin sulfate glycosaminoglycans. Role of N-linked oligosaccharide addition, trimming, and processing. 249 82

Regulation of glucose degradation in both yeasts and tumor cells is very similar in many respects. In both cases it leads to excretion of intermediary metabolites (e.g., ethanol, lactate) in those cell types where uptake of glucose is unrestricted (Saccharomyces cerevisiae, Bowes melanoma cells). The similarities between glucose metabolism observed in yeast and tumor cells is explained by the fact that cell transformation of animal cells leads to inadequate expression of (proto-)oncogenes, which force the cell to enter the cell cycle. These events are accompanied by alterations at the signal transduction level, a marked increase of glucose transporter synthesis, enhancement of glycolytic key enzyme activities, and slightly reduced respiration of the tumor cell. In relation to homologous glucose degradation found in yeast and tumor cells there exist strong similarities on the level of cell division cycle genes, signal transduction and regulation of glycolytic key enzymes. It has been demonstrated that ethanol and lactate excretion in yeast and tumor cells, respectively, result from an overflow reaction at the point of pyruvate that is due to a carbon flux exceeding the capacity of oxidative breakdown. Therefore, the respiratory capacity of a cell determines the amount of glycolytic breakdown products if ample glucose is available. This restricted flux is also referred to as the respiratory bottleneck. The expression "catabolite repression", which is often used in textbooks to explain ethanol and acid excretion, should be abandoned, unless specific mechanisms can be demonstrated. Furthermore, it was shown that maximum respiration and growth rates are only obtained under optimum culture conditions, where the carbon source is limiting.
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PMID:Metabolic control of glucose degradation in yeast and tumor cells. 251 Apr 72

Fotemustine (S 10036) is a new nitrosourea compound whose antitumoral activity has been demonstrated, particularly in disseminated malignant melanoma. Pharmacokinetic parameters of this drug were investigated during phase II clinical trials and compared according to tumor type. Twenty-six patients entered the study and received an induction treatment (weekly 100 mg/sq.m of fotemustine in 250 ml of 5% glucose in water over a one-hour IV infusion for 3 consecutive weeks) followed by a 4-week rest period. A maintenance therapy (100 mg/sq.m every three weeks) was proposed in stabilized or responsive patients. Plasmatic assay of fotemustine was carried out by HPLC. Seventy-one cycles were analyzed. A short half-life and a large intra and inter-individual variability of all kinetic parameters (especially plasmatic clearance) was found independent of tumour type. The study of patient's clinical behaviour was shown to be related to the clearance value obtained during the first treatment cycle which seems to predict the clinical response in the case of malignant melanoma. This finding needs to be confirmed in a larger number of patients and in other tumor localizations.
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PMID:[Study of the clinical pharmacokinetics of fotemustine in various tumor indications]. 263 34

A strain of Gram negative bacteria was isolated from the surface soil of Wuying Hill at Jinan, Shandong province with Gause's medium in 1973. It is a strain of antagonistic bacteria for hysterocervicoma, hepatoma and melanoma of mice screened from 2100 strains of bacteria. It is also antagonistic to Staphylococcus aureus, Bacillus subtilis and Micrococcus. It is a Gram negative bacterium with lophotrichous polar flagella. Straight rods in shape or with a little slightly curved rods, 0.5-0.6 X 1-2 microns, randomly arranged, poly-beta-hydroxybutyrate granules are accumulated in cells after 2-5 days cultivation. Water green soluble pigment and green fluorescent pigment are produced. Respiratory metabolism, chemoorganotroph, many carbon-containing organic compounds can be used as carbon sources, such as glucose, trehalose, ethanol, cellulobiose, fucose, arginine and betaine, but propionic acid or tartaric acid is not utilized. Inorganic nitrogen containing compounds can be used ae the sole source of nitrogen. No growth factor is necessary for growth. Gelatin is hydrolyzed. Starch and cellulose are not hydrolyzed. Nitrate is not reduced. Arginine dihydrolase is produced. Levan is produced from sucrose. Growth occurs from 7 degrees C to 37 degrees C and from pH 5.65-8.40. No growth occurs at 40 degrees C and at pH value below 4.86. It can not grow autotrophically with hydrogen. Its G + C contents in DNA is 58.1 mol%. DNA-DNA hybridization experiments reveals a relatedness value of 58.6% between this strain and Ps. fluorescens. The above evidence shows that this strain differs from all species known in Pseudomonas, such as Pseudomonas fluorescens group. Pseudomonas caryophylli, Pseudomonas cepacia, Pseudomonas marginata, Pseudomonas acidovorans, Pseudomonas testosteroni and Pseudomonas delafieldii.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A sarcoma-static new species of Pseudomonas, Pseudomonas jinanensis sp. nov]. 278 86

Trehalose-6,6'-dimycolate (TDM) and its monosaccharide-type analogues were synthesized, and their lethal and adjuvant activities were examined in mice. All the monosaccharide-type analogues with a glucose or N-acetylglucosamine moiety were devoid of lethal toxicity to mice; in particular, D-GlcNAcM(1-deoxy) and D-GlcNM did not cause any loss of body weight at an early stage after intravenous administration as a 9% oil-in-water emulsion. Intraperitoneal administration of D-GlcNAcM(1-deoxy) in aqueous suspension, as well as TDM, could activate macrophages to become tumoricidal against tumour cells, whereas D-GlcNAcM(1-deoxy) in oil emulsion, unlike TDM, caused no granulomatous formation in the lung after intravenous injection. Squalane-treated D-GlcNAcM(1-deoxy) showed significant inhibition of spontaneous lung metastases by B16-BL6 melanoma cells when it was administered twice intratumorally. The non-toxic monosaccharide-type analogue of TDM [D-GlcNAcM(1-deoxy)] was a beneficial adjuvant for the activation of macrophages and the prevention of cancer metastasis.
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PMID:Lethal toxicity and adjuvant activities of synthetic TDM and its related compounds in mice. 278 60

Flow cytometry was used to measure cytoplasmic pH (pHi) of B16 melanoma cells taken from tumor-bearing animals. We used a ratiometric method to allow measurements on an individual cell basis which were independent of cellular content of the pH indicator BCECF. In order to "freeze" any intercell variance which may have existed within the tumor mass, tumors were mechanically disaggregated in bicarbonate-free medium containing 0.5 mM amiloride at 4 degrees C and loaded with BCECF in choline chloride-based Earle's solution at 37 degrees C. Studies using cells grown in vitro showed that this protocol prevented acid load recovery during the 30-min period typically required between tumor excision and pHi measurement. A calibration curve was obtained by resuspending BCECF-stained cells in a range of buffers containing the proton ionophore nigericin. The range of values for individual cells was estimated by comparing the coefficient of variation of the test sample with that obtained when nigericin was used to reduce all cells to the pHi of the calibration buffer. The average value for mean tumor cell pH was 7.32 +/- 0.05 SD. Pretreatment of animals with intraperitoneal glucose for one hour resulted in an average for mean pHi of 7.17 +/- 0.17 SD. Mean coefficient of variation was 8.7%, and in the presence of nigericin, 8.1%. These values indicate a variance in measured pHi of approximately +/- 0.4 pH units, but most of this results from experimental error rather than true intercell pHi variance. The method used here is capable of detecting reduction in mean tumour pHi caused by ip glucose, but incapable of precise estimation of individual cell values. Despite these uncertainties, the results suggest that the range of pHi within B 16 tumors is small.
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PMID:Flow cytometric measurement of intracellular pH in B16 tumors: intercell variance and effects of pretreatment with glucose. 290 83

The effect of insulin on glucose metabolism through different pathways and the glucose transporters in Harding-Passey melanoma cells have been studied. Glucose was utilized at a rate of 6.9 +/- 2.3 (SD) mumol X g-1 X h-1 with 86% transformed into lactate and pyruvate and only 0.43 and 3% metabolized through the tricarboxylic acid cycle and the pentose phosphate pathway, respectively. Of the total glucose consumed 2% was used in protein synthesis and 2% was used for lipid synthesis. Hexokinase isoenzyme was type I and enolase was present mainly in the alpha gamma hybrid form. The glucose transporters were cytochalasin B sensitive. The number of high affinity cytochalasin B binding sites was 175,000 receptors/cell (about 0.6 pmol/mg protein) and Kd = 1 X 10(-7) M. Insulin increased glucose utilization and lactate production by about 70% and caused a 56% increase in transport without alterations in the Kd of the site. Insulin receptors were quantified by binding assay using 125I-insulin. Kd was 11 X 10(-9) M with the number of receptors calculated as 11,500/cell. Harding-Passey melanoma cells could thus be a useful model to study basic metabolic events and their modulation by hormones or other effectors.
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PMID:Effects of insulin on glucose transporters and metabolic patterns in Harding-Passey melanoma cells. 308 79

Enhancement of the potency and melanoma-selectivity of redox agents was sought by two different approaches. In screening a series of catechols, derivatives of moderate half-life (dopa, dopamine, noradrenaline, 3,4-dihydroxybenzylamine, 3,4-dihydroxyphenylacetic acid; t1/2 12-33 hr) had significant toxicity (D37 20-30 microM) and selectivity for melanoma cells compared with HeLa. Less stable catechols (5-hydroxy- and 6-hydroxydopamine; t1/2 4 and 5 hr respectively) were toxic but lacked selectivity whereas more stable derivatives (4-hydroxyanisole, 2,3-dihydroxybenzoic acid; t1/2 greater than 72 hr) were less potent (D37 greater than 100 microM) and had poor selectivity. Gossypol, a complex catechol derivative, exhibited significant toxicity (D37 7.7 microM) but little selectivity. Enzymes capable of reacting with components of the culture medium and known to continuously generate hydrogen peroxide (glucose-6-oxidase) or superoxide ion (xanthine oxidase) exhibited a similar degree of selectivity as dopa, indicating that active oxygen species are more important mediators of catechol toxicity than quinones. Rhodamine 123, a cationic dye preferentially taken up by some tumour cells, was accumulated equally by melanoma and HeLa yet had a similar selectivity to that of dopa. In the second approach, the potency of dopa was found to be greatly enhanced during early S phase. This phenomenon, found with cells synchronised both by mitotic shake off and by 24 hr accumulation in G1S in the presence of 5 mM hydroxyurea, occurred during a period in which the proportion of cells in S phase cells was low. These results indicate that human cells are extremely sensitive to extracellular active oxygen species during a relatively short period in early S phase, and selective killing of asynchronous melanoma cells therefore requires agents capable of sustaining a redox effect for at least one cell cycle.
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PMID:Potency, selectivity and cell cycle dependence of catechols in human tumour cells in vitro. 313 76

Hyperthermia induces conformational changes of macromolecular structures. Such effects lead to a sudden inhibition of DNA, RNA and protein synthesis and a breakdown of membranes and of the cytoskeleton. These alterations can be very important for the mechanism of cell killing by hyperthermia. Furthermore hyperthermia induces a number of immediate metabolic changes by increasing metabolic rates. These alterations have been studied especially in intermediary metabolism like glycolysis, citrate cycle, lipid metabolism and oxidative phosphorylation. An increased turnover of ATP has been observed in cells and tissues during heating. These changes lead to a depletion of energy reservoirs. Also, disregulations occur at certain metabolic key points. Thus, the pathway of pyruvate into the citrate cycle via acetyl-CoA is apparently reduced in heated melanoma cells in vitro. The redox ratios of lactate/pyruvate, NADH/NAD+ and others are decreased. When the same melanoma cells are grown as a xenograft on nude mice the metabolic rates are also enhanced; however, the lactate/pyruvate ratio increases during a localized heating of the tumour. The extent of this effect is very variable in individual tumours and is apparently correlated with the blood flow. These alterations can be enhanced by glucose loading and can be used as an indicator of hypoxia within the tumour. Thus, the micromilieu can be modified by these metabolic effects in such a way that the thermosensitivity is increased. The data show that metabolic processes are directly and indirectly involved in cell killing by hyperthermia.
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PMID:Aspects of metabolic change after hyperthermia. 328 23

The substitution of glucose-antiglucose oxidase complex (GAG) for peroxidase antiperoxidase (PAP) in the Sternberger three-layer unlabeled antibody method avoids the problems associated with the use of the chromogen 3,3,diaminobenzidine (DAB). The blue final reaction product obtained using the GAG complex is not obscured by melanin granules, which is often the case when using the PAP-DAB combination. The replacement of PAP with GAG complexes facilitates the detection of melanocytes in melanoma and blue nevi. The absence of endogenous glucose oxidase in mammals provides for greater image contrast, which is not possible using alternative chromogens and immunoperoxidase.
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PMID:The substitution of glucose-antiglucose oxidase complex (GAG) for peroxidase-antiperoxidase (PAP) in immunohistochemical studies of skin. 330 93


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