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

Cytotoxin P4 was isolated from the venom of Naja nigricollis nigricollis in three steps and contained 55% of the crude cytotoxic activity. It had a molecular weight of 8 KD, was stable over a pH range of 1-11 and in boiling water for at least 15 min. It had no measurable enzymatic activities, but was destroyed by proteases. Concentrations of 0.8, 1, 1.2, 25. 20 and 45 ug/ml, were needed to destroy murine melanoma B16 and WEHI 3B leukemia, rat chondrosarcoma, mouse erythrocytes and spleen cells, and human erythrocytes, respectively, thereby showing preferential cytotoxicity to the examined tumor cells. It also prevented the development of the melanoma, leukemia and chondrosarcoma tumors in vivo when mixed with the cells prior to the injection into the animal.
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PMID:Isolation and characterization of a cytotoxin P4 from the venom of Naja nigricollis nigricollis preferentially active on tumor cells. 177 20

This report describes the development, characterization and preclinical efficacy evaluation of water soluble glucan sulfate. Glucan sulfate was derived from insoluble beta-1,3-D-glucan isolated from Saccharomyces cerevisiae. The proposed repeating unit empirical formula of glucan sulfate is [(C6H10O5)5.3H2SO4]n. Two polymer peaks were resolved by aqueous high-performance size exclusion chromatography (HPSEC) with on-line multi-angle laser light scattering (MALLS) photometry and differential viscometry. Peak 1 (MW = 1219697 Da) represents approximately 1% of the total polymers, while peak 2 (MW = 8884 Da) accounts for approximately 99% of polymers. 13C-NMR spectroscopy suggests that glucan sulfate polymer strands may be partially cross-linked. Glucan sulfate (250 mg/kg, i.v.) increased (P less than 0.01) macrophage vascular clearance of 131I-reticuloendothelial emulsion by 42% (P less than 0.01) and in vitro bone marrow proliferation by 46% (P less than 0.05). Glucan sulfate (250 mg/kg, i.v.) increased (P less than 0.05) median survival time of C57B1/6J mice with syngeneic melanoma B16 or sarcoma M5076. In addition, glucan sulfate immunoprophylaxis increased resistance of mice to challenge with Escherichia coli, Candida albicans or Mouse Hepatitis Virus strain A-59. We concluded that: (1) insoluble beta-1,3-D-glucan can be converted to a water soluble sulfated form; (2) glucan sulfate activates macrophages and stimulates bone marrow; (3) glucan sulfate exerts antitumor therapeutic activity, and (4) glucan sulfate immunoprophylaxis will modify the course of experimental infectious disease.
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PMID:Development, physicochemical characterization and preclinical efficacy evaluation of a water soluble glucan sulfate derived from Saccharomyces cerevisiae. 177 55

The rate of oxidation by purified mushroom tyrosinase of 30 compounds was measured by oximetry, and the tyrosinase-dependent cytotoxicity of each estimated in an in vitro assay using exposure of non-melanogenic cells to the agents in the presence and absence of tyrosinase. Cytotoxicity was estimated by immediate inhibition of DNA synthesis; 4-hydroxyanisole was used as the reference material. Compounds that were not oxidized by tyrosinase were found to be non-toxic but there was no direct relationship between the rate of oxidation and the relative cytotoxicity of those materials that acted as substrates for the enzyme. Thioethers were found to be more cytotoxic than the corresponding phenoxyethers. This was partly due to their greater rate of oxidation by tyrosinase and, in the case of propylthiophenol, the consequence of higher effective toxicity of the lipophilic species. The optimum chain length for the side chain of the oxyethers was three saturated carbon atoms and the toxicity appeared to be influenced by the lipophilicity of the compounds, possibly reflecting the relative lipid solubility of the putative toxic ortho-quinones generated from them. The maximum tyrosinase-dependent toxicity observed was in the range 5-6 times the relative toxicity of 4-hydroxyanisole. Sulphinyl and sulphonyl derivatives were inactive. In addition to oxyethers and thioethers, esters and glycosides of oxyethers were also examined and were found to be toxic in the presence of tyrosinase when hydrolysed. The succinates were found to be oxidized and toxic in our test system, suggesting that they rapidly underwent spontaneous hydrolysis. Oximetry data suggest that slight spontaneous hydrolysis of the other compounds occurs but they were not toxic in our assay. Ring-methylated phenoxyethers were oxidized relatively slowly and were non-toxic. Fluorine-substituted phenoxyethers were oxidized slightly more rapidly and exhibited clear toxicity in our system. Sesamol was oxidized to a black pigment but was non-toxic in our assay. A water-soluble vitamin E derivative was not oxidized and was non-toxic. Allyl hydroquinone was not oxidized but exhibited significant direct toxicity.
Melanoma Res
PMID:In vitro assessment of the structure-activity relationship of tyrosinase-dependent cytotoxicity of a series of substituted phenols. 182 34

Two synthetic, water-soluble porphyrins, tetra-4N-methyl-pyridyl porphyrin (T4NMPyP) and tetra-N,N,N-trimethylanilinium porphyrin (TMAnP), and their indium(III) complexes have been isotopically substituted for evaluation by solid-state NMR of their adsorption to melanin. Methyl carbons on the pyridyl and anilinium nitrogens on the periphery of the porphyrin are one site of substitution; the four equivalent meso carbons in the porphyrin ring are the second. Chemical shifts and line widths of the carbon resonances in the bulk porphyrins change after they are adsorbed on synthetic and natural melanins. These changes may be related to the predominant binding interactions involved in the adsorption process and suggest that chemisorption, involving strong interactions comparable to chemical bonds, occurs between charged groups in both ligand and substrate. Inhomogeneous line broadening of the resonances implies that variations in binding exist, which is in keeping with the known heterogeneous nature of the melanin polymer and the different steric demands of the porphyrin ligands. These solid-phase experiments illustrate the promise of NMR for elucidating information about the binding of soluble molecules to insoluble and structurally irregular biopolymers. Furthermore, they represent the first spectroscopic probe of the binding of cationic molecules to the biopolymer melanin in the solid state. Coupled with results from molecular modelling, they indicate that cationic porphyrins bind to melanin at similar sites.
Melanoma Res
PMID:Analysis of spectral changes in isotopically substituted porphyrins adsorbed on melanin surfaces by solid-state carbon-13 nuclear magnetic resonance spectroscopy. 184 16

Beta emitting 106Ru-applicators are used to treat choroidal melanoma. In order to improve the accuracy and simplify the dosimetry of these applicators, the suitability of using a p-type silicon semiconductor detector has been investigated. The detector is calibrated in a low energy electron beam. An important property of the detector for this application is that the linear scattering power of the epoxy resin that surrounds the silicon crystal is within 1% of that for water, in the energy interval of interest. Furthermore the variation in the mass collision stopping power ratio water to silicon is within 4% in this energy interval. The accuracy of the dose-rate measured with the detector is about 5% for this application.
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PMID:Dosimetry of 106Ru eye applicators with a p-type silicon detector. 188 30

Herein we describe the isolation, physicochemical characterization and preclinical evaluation of a water-soluble biologic response modifier extracted from Sclerotium glucanicum. Alkaline extraction of insoluble S. glucanicum exopolymers produced a soluble scleroglucan composed of a triple-helical beta-1,3-linked glucopyranose backbone with single beta-1,6-linked glucopyranosyl branches every third subunit. Scleroglucan has a weight average molecular mass of 1.56 x 10(6) Da, a weight average root mean square distance from the center of gravity of the molecule to its farthest elements of 51.8 nm, a polydispersity (weight-average molecular mass/number average molecular mass) of 1.83 and intrinsic viscosity of 3.081 dl/g. Scleroglucan (250 mg/kg, intravenously) stimulated in vivo murine macrophage phagocytic activity (66%, P less than .001) and increased in vitro macrophage tumor cytotoxicity against syngeneic tumor targets by 124% (P less than .05). Scleroglucan enhanced (P less than .001) murine bone marrow proliferation in a biphasic manner by up to 328%. Scleroglucan therapy increased survival of mice challenged with syngeneic lymphoma, melanoma or adenocarcinoma. AKR/J mice bearing syngeneic lymphoma (1 x 10(3) cells, intraperitoneally) demonstrated increased (P less than .001) long-term survival (100% vs. 0%, greater than 64 days). C57Bl/6J mice bearing syngeneic melanoma B16 (5 x 10(5) cells, subcutaneously) demonstrated increased long-term survival (64% vs. 0%, P less than .05). C57Bl/6J mice bearing syngeneic adenocarcinoma BW10232 (1 x 10(5) cells, subcutaneously) demonstrated increased (P less than .05) median survival time. In addition, scleroglucan prophylaxis increased resistance of mice to challenge with Staphylococcus aureus, Candida albicans and mouse hepatitis virus A-59. Scleroglucan did not induce toxicity or hepatomegaly. We conclude that: 1) a branched, water-soluble beta-1,3-linked scleroglucan biologic response modifier can be extracted from S. glucanicum; 2) scleroglucan will stimulate immunity, modify experimental neoplastic disease and increase resistance to microbial challenge; and 3) scleroglucan shows promise as an immunopotentiating drug.
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PMID:Isolation, physicochemical characterization and preclinical efficacy evaluation of soluble scleroglucan. 190 59

Sodium ascorbate supplementation in drinking water inhibited subcutaneous tumor growth, enhanced levodopa methylester (LDME) chemotherapy, and increased survival of B16 melanoma-bearing mice. Antitumor activity was greatest in mice fed diets low in tyrosine and phenylalanine (restricted diet). Ascorbate partially protected against LDME-induced decrease in food intake. Primary tumor masses were smaller, more well defined, and less invasive in ascorbate-supplemented mice, and secondary tumor masses appeared encapsulated. Dehydroascorbate increased tumor growth and decreased survival. Ascorbate supplementation did not alter establishment of experimental B16-BL6 melanoma metastases but inhibited tumor outgrowth when combined with LDME chemotherapy and the restricted diet. Spontaneous metastasis was inhibited by ascorbate in mice fed the restricted diet. Ascorbate supplementation doubled plasma concentration in melanoma-bearing mice independent of diet and increased tumor concentration 3.7-fold (basal diet) and 5.6-fold (restricted diet) relative to unsupplemented mice. Tumor peroxidation also increased during ascorbate supplementation and LDME treatment.
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PMID:Ascorbate in the treatment of experimental transplanted melanoma. 196 84

By bioactivity-directed fractionation, six cytotoxic constituents have been characterized from the bark of Plumeria rubra collected in Indonesia. Three iridoids, fulvoplumierin [1], allamcin [2], and allamandin [3], as well as 2,5-dimethoxy-p-benzoquinone [4], were found to be active constituents of the P. rubra petroleum-ether- and CHCl3-soluble extracts. Cytotoxic compounds isolated from the H2O-soluble extract of the bark were the iridoid plumericin [5], and the lignan liriodendrin [6]. Each of these substances was found to demonstrate general cytotoxic activity when evaluated with a panel of cell lines composed of murine lymphocytic leukemia (P-388) and a number of human cancer cell-types (breast, colon, fibrosarcoma, lung, melanoma, KB). Five additional iridoids, 15-demethylplumieride [7], plumieride [8], alpha-allamcidin [9], beta-allamcidin [10], and 13-O-trans-p-coumaroylplumieride [11], were obtained as inactive constituents. Compound 7 was found to be a novel natural product, and its structure was determined by spectroscopic methods and by conversion to plumieride [8]. The configuration of the C-4 stereocenter was unambiguously assigned for compounds 9 and 10, and certain nmr reassignments have been provided for compound 1.
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PMID:Cytotoxic constituents of the bark of Plumeria rubra collected in Indonesia. 196

MR imaging has been performed on malignant melanomas in vitro and in vivo. Changes of the water content in an enucleated malignant melanoma in vitro were followed by significant changes of the T1 and T2 values. In mice with implanted subcutaneous melanoma similar changes could be obtained after injection of glucose and fructose intraperitoneally. Malignant melanoma of the eye could be influenced in the same way in 10 consecutive patients after oral intake of glucose and fructose. The present study shows that the MR images may be significantly changed after a few hours by altered metabolism induced by glucose and fructose. It is anticipated that this is due to changes within the tumor leading to different water distribution. The finding may be of importance as a further help for diagnosing malignant melanoma of the eye.
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PMID:Changes in MR of malignant melanomas induced by glucose and fructose. A clinical and experimental investigation. 206 64

We have shown that macrophage-derived prostaglandin (PG)E2 inactivates all interleukin 2 (IL-2) dependent killer cell lineages in the tumor-bearing host, so that chronic indomethacin therapy (CIT) combined with multiple rounds of IL-2 can cure experimental and spontaneous metastases of a variety of murine tumors. We tested the efficacy of this therapy on experimental human melanoma metastasis in nude mice and characterized the killer cells generated in situ. BALB/c nude mice were injected i.v. with 2 x 10(6) human lung-metastasizing line P52, MeWo melanoma cells. After 5 weeks, when lung nodules were well established, mice received vehicles alone (control) or were given (a) CIT (14 micrograms/ml in drinking water); (b) three rounds of IL-2, 25,000 Cetus U, 8 hourly i.p. (days 40-44, 50-54, 60-64); (c) CIT + three rounds of IL-2; (d) CIT + four rounds of IL-2 (round 4 on days 70-74); and (e) CIT + five rounds of IL-2 (round 5 on days 80-84). Control and experimental mice were killed on day 71 to score lung colonies and evaluate killer activity in splenic and lung lymphocytes and macrophages against murine YAC-1 lymphoma and B16F10 melanoma, human P52 melanoma, K562 erythroleukemia, and Raji lymphoma targets. Killer cells for P52 were phenotyped for Thy-1, Lyt-2, and asialo-GM-1 markers by ab + C'-mediated deletion of killer function. Mice in all groups were also kept for survival. CIT alone improved splenic NK activity but marginally reduced the lung colony counts or prolonged the survival time. Three rounds of IL-2 alone reduced the median colony counts by 50% and prolonged the survival by 2 weeks, but resulted in no long-term, disease-free survival, in spite of significant activation of LAK cells with Thy-1-, Lyt-2-, AGM-1+ phenotype in the spleen. CIT + 3 rounds of IL-2 reduced the median colony counts from 40 to 0 and improved the survival from a median of 66 (control) to 120 days (40% surviving 260 + days). CIT + four or five rounds of IL-2 caused long-term (260 + days) survival of 80% mice, most surviving 400 + days. The combination therapy activated killer lymphocytes (Thy-1-, Lyt-2-, AGM-1+) and, to a smaller extent, macrophages (AGM-1 +/-) in the spleen and the lungs, showing a high cytocidal ability for all the targets.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cure of human melanoma lung metastases in nude mice with chronic indomethacin therapy combined with multiple rounds of IL-2: characteristics of killer cells generated in situ. 209 Jan 99


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