Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A glycolipid antigen, detected by a monoclonal antibody (ME 311) obtained by immunizing mice with a human metastatic melanoma cell line (WM 46), was isolated and structurally characterized. Using immunostaining on thin-layer chromatograms for monitoring, 1.0 mg of a pure alkali-labile disialoganglioside was obtained from 23 g of packed melanoma cells (WM 164). Fractionation of the lipid extract was done on DEAE-Sepharose columns into total disialogangliosides which were repeatedly separated by high-pressure liquid chromatography. On mild alkaline treatment, the ganglioside was converted to a slower migrating species identical with a ganglioside GD3 isolated from the same source (Neu5Ac alpha 2----8Neu5Ac alpha 2----3Gal beta 1----4Glc beta 1----1-cer-amide) and specifically detected by monoclonal antibody R24. Comparison of the two gangliosides by fast-atom bombardment mass spectrometry (revealing an acetyl group on the terminal sialic acid on the alkali-labile species) and by 1H NMR (indicating the position of the acetyl group) suggested the following structure: Neu5,9Ac2 alpha 2----8Neu5Ac alpha 2----3Gal beta 1----4Glc beta 1----1-ceramide. This is identical with a ganglioside proposed earlier to exist in melanoma cells (Cheresh, D. A., Varki, A. P., Varki, N. M., Stallcup, W. B., Levine, J., and Reisfeld, R. A. (1984) J. Biol. Chem. 259, 7453-7459). Immunostaining with ME 311 antibody of cell extracts on thin-layer chromatography chromatograms revealed only this ganglioside in the melanoma cells, while normal human brain was negative. However, in one of the total ganglioside extracts tested for presence of binding with antibody ME 311, three gangliosides were found to bind. No evidence was obtained for the presence of the antigenic epitope in mucins or glycoproteins of the melanoma cells.
 ...
PMID:Proton NMR and fast-atom bombardment mass spectrometry analysis of the melanoma-associated ganglioside 9-O-acetyl-GD3. 405 89

The alterations caused on the structure of melanins by acid and alkaline extraction methods were studied by means of techniques such as Fourier Transform Infrared spectroscopy and thermogravimetry. Acid extraction results in the hydrolysis of aromatic monomers of the pigment, leading to uncyclicized residues and to a less conjugated polymer. Alkaline methods catalyse the covalent binding of proteins present in the melanin extract, thus leading to melanoprotein artifacts. A new method based on the delipidation with ether and deproteinization with SDS of previously isolated melanosomes is proposed. This method shows that melanins present in Harding-Passey mouse melanoma have a bound protein moiety, so that they should exist "in vivo" as melanoprotein complexes. Thermogravimetric data suggest that the chromogen moiety of the melanoproteins in Harding-Passey mouse melanoma is a mixture of eu- and pheomelanins.
Physiol Chem Phys Med NMR 1985
PMID:FT-IR spectroscopy of natural melanins isolated from Harding-Passey mouse melanoma. 408 Aug 27

Prostaglandin D2 spontaneously decomposes at physiological pH and temperature to 9-deoxy-delta 9-PGD2 (designated PGJ2). We developed a TLC procedure for the isolation of PGJ2 which was identified by both proton-NMR and mass spectrometry. Freshly prepared PGJ2 was active in inhibiting aggregation induced by ADP in citrated human platelet rich plasma. As reported by Fukushima et al. (1). PGJ2 was less active (x 0.1-0.25) than PGD2 as an inhibitor. Concentrations of PGJ2 that markedly inhibited aggregation of human platelets were generally incapable of inhibiting aggregation of rat or guinea pig platelets. Using a heterologous system of human platelets mixed with guinea pig plasma samples (2), it was shown that the ability of PGJ2 to inhibit platelet aggregation was lost immediately following intravenous injection in anesthetized guinea pigs. This apparent rapid uptake and/or degradation of PGJ2 might also explain why PGJ2 had no effect on blood pressure of anesthetized guinea pigs. PGJ2 was potent in inhibiting proliferation of cultured vascular smooth muscle cells, mouse melanoma cells and mouse fibroblasts. Less potent anti-proliferative effects were seen with two other degradation products of PGD2, one of which was the delta 12 metabolite reported (3,4) to be formed from PGJ2 in a reaction catalyzed by serum albumin.
 ...
PMID:On the identification and biological properties of prostaglandin J2. 659 46

We have used an Escherichia coli expression system to produce forms of vascular cell-adhesion molecule-1 (VCAM-1) containing the first two and three supposed immunoglobulin-like domains. A form consisting of the first two domains of VCAM-1 is shown to promote very-late antigen-4-dependent spreading of a melanoma cell line comparable to that found for the equivalent region in the full seven-domain form. Preliminary structural analysis by CD and NMR is consistent with an immunoglobulin fold which is predicted from sequence comparison studies.
 ...
PMID:Expression and characterisation of a very-late antigen-4 (alpha 4 beta 1) integrin-binding fragment of vascular cell-adhesion molecule-1. 752 40

1H NMR has been used to investigate the structural properties of RANTES, a protein from the C-C branch of the chemotactic cytokine family that has a strong chemoattractive effect on monocytes, lymphocytes, and eosinophils. Titration of pH from 5.0 to 2.5 indicates that RANTES is extensively aggregated in solution above pH 4.0. At pH 3.7 the protein is mostly dimeric, although this species does dissociate to the monomer with a Kd of 35 microM. NMR data have been acquired and resonance assignments made for the dimeric species. Structures of the dimer have been generated by distance geometry and simulated annealing calculations that utilized 1956 intramolecular distance restraints, 120 intermolecular distance restraints, 164 dihedral angle restraints, and 68 restraints enforcing 34 hydrogen bonds (17.0 restraints per residue). The structure is well-defined (average root mean square deviation from the average structure of 0.38 +/- 0.06 and 0.53 +/- 0.12 A for backbone heavy atoms of residues 4-66 of the monomer and dimer, respectively). Each monomer consists of a C-terminal alpha-helix packing against a three-stranded antiparallel beta-sheet and two short N-terminal beta-strands; dimerization occurs between the N-terminal regions of each monomer. This quaternary structure is very different from that of the C-X-C chemokines such as interleukin-8 and melanoma growth stimulatory activity but similar to that found for the C-C chemokine macrophage inflammatory factor 1 beta. Distinct structural differences between RANTES and other chemokines at both the tertiary and quaternary level are discussed with regard to the distinct biological functions of the C-C and C-X-C members of this protein family.
 ...
PMID:Proton NMR assignments and solution conformation of RANTES, a chemokine of the C-C type. 753 88

The concentration of phospholipid metabolites in tumours has been hypothesized to be related to rate of cell membrane turnover and may reflect rate of cell proliferation. The purpose of the study reported here was to investigate whether 31P NMR resonance ratios involving the phosphomonoester (PME) or phosphodiester (PDE) resonance are correlated to fraction of cells in S-phase or volume-doubling time in experimental tumours. Four human melanoma xenograft lines (BEX-t, HUX-t, SAX-t, WIX-t) were included in the study. The tumours were grown subcutaneously in male BALB/c-nu/nu mice. 31P NMR spectroscopy was performed at a magnetic field strength of 4.7 T. Fraction of cells in S-phase was measured by flow cytometry. Tumour volume-doubling time was determined by Gompertzian analysis of volumetric growth data. BEX-t and SAX-t tumours differed in fraction of cells in S-phase and volume-doubling time, but showed similar 31P NMR resonance ratios. BEX-t and WIX-t tumours showed significantly different 31P NMR resonance ratios but similar fractions of cells in S-phase. The 31P NMR resonance ratios were significantly different for small and large HUX-t tumours even though fraction of cells in S-phase and volume-doubling time did not differ with tumour volume. None of the 31P NMR resonance ratios showed significant increase with increasing fraction of cells in S-phase or significant decrease with increasing tumour volume-doubling time across the four xenograft lines.(ABSTRACT TRUNCATED AT 250 WORDS)
NMR Biomed 1995 Apr
PMID:31P NMR spectroscopy studies of phospholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation. 754 88

The syntheses of furan and thiophene analogues of tiazofurin (furanfurin and thiophenfurin, respectively) are described. Direct stannic chloride-catalyzed C-glycosylation of ethyl 3-furan-carboxylate (6) or ethyl 3-thiophencarboxylate (18) with 1,2,3,5-tetra-O-acetyl-D-ribofuranose gave 2- and 5-glycosylated regioisomers, as a mixture of alpha- and beta-anomers, and the beta-2,5-diglycosylated derivatives. Deprotection of ethyl 5-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)furan-3-carboxylate (9 beta) and ethyl 5-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)thiophene-3-carboxylate (20 beta) with sodium ethoxide afforded ethyl 5-beta-D-ribofuranosylfuran-3-carboxylate (12 beta) and ethyl 5-beta-D-ribofuranosylthiophene-3-carboxylate (23 beta) which were converted into 5-beta-D-ribofuranosylfuran-3-carboxamide (furanfurin, 4) and 5-beta-D-ribofuranosylthiophene-3-carboxamide (thiophenfurin, 5) by reaction with ammonium hydroxide. The anomeric configuration and the site of glycosylation were established by 1H-NMR and proton-proton nuclear Overhauser effect difference spectroscopy. The structure of compound 23 beta was confirmed by X-ray crystallography. Thiophenfurin was found to be cytotoxic in vitro toward murine lymphocytic leukemia P388 and L1210, human myelogenous leukemia K562, human promyelocytic leukemia HL-60, human colon adenocarcinoma LoVo, and B16 melanoma at concentrations similar to that of tiazofurin. In the same test furanfurin proved to be inactive. Thiophenfurin was found active in vivo in BD2F1 mice inoculated with L1210 cells with a % T/C of 168 at 25 mg/kg. K562 cells incubation with thiophenfurin resulted in inhibition of inosine monophosphate (IMP) dehydrogenase (63%) and an increase in IMP pools (6-fold) with a concurrent decrease in GTP levels (42%). Incubation of adenosine-labeled K562 cells with tiazofurin, thiophenfurin, and furanfurin resulted in a 2-fold higher NAD analogue formulation by thiophenfurin than by tiazofurin. Furanfurin was converted to the NAD analogue with only 10% efficiency. The results obtained support the hypothesis that the presence of S in the heterocycle in position 2 with respect to the glycosidic bond is essential for the cytotoxicity and IMP dehydrogenase activity of tiazofurin, while the N atom is not.
 ...
PMID:Furanfurin and thiophenfurin: two novel tiazofurin analogues. Synthesis, structure, antitumor activity, and interactions with inosine monophosphate dehydrogenase. 756 14

beta-Xylosides compete with endogenous proteoglycan core proteins and act as alternate acceptors for synthesizing protein-free glycosaminoglycan chains. Their assembly on these alternate acceptors utilizes the same glycosyltransferases that make the protein-bound chains. Most studies using alternate acceptors focus on the production of sulfated glycosaminoglycan chains that are thought to be the major products. However, we previously showed that labeling melanoma cells with [6-3H]galactose in the presence of 4-methylumbelliferyl (MU) or p-nitrophenyl (pNP) beta-xylosides led to the synthesis of mostly di- to tetrasaccharide products including incomplete core structures. We have solved the structure of one of the previously unidentified products as, GalNAc alpha(1,4)GlcA beta(1,3)Gal beta(1,3)Gal beta(1,4)Xyl beta MU, based on compositional analysis by high performance liquid chromatography, fast atom bombardment, electrospray mass spectrometry, and one-dimensional and two-dimensional 1H NMR spectroscopy. The novel aspect of this molecule is the presence of a terminal alpha-Gal-NAc residue at a position that is normally occupied by beta-GalNAc in chondroitin/dermatan sulfate or by alpha-Glc-NAc in heparin or heparan sulfate chains. An alpha-GalNAc residue at this critical location may prevent further chain extension or influence the type of chain subsequently added to the common tetrasaccharide core.
 ...
PMID:Identification of a novel glycosaminoglycan core-like molecule. I. 500 MHz 1H NMR analysis using a nano-NMR probe indicates the presence of a terminal alpha-GalNAc residue capping 4-methylumbelliferyl-beta-D-xylosides. 772 30

The Cesium salt of BSSB (Cs4B24H22S2), a common boron-neutron-capture-therapy (BNCT) agent, was injected into M2R mouse melanoma xenografts, and detected in vivo by 1H-observed, 10B-edited NMR spectroscopy. The technique of spin-echo difference spectroscopy, in which a proton spin-echo is detected following the alternating presence and absence of a 10B 180 degrees pulse was used. This method provides much higher sensitivity than direct 10B NMR detection, and should thus be suitable for in vivo detection in patients about to undergo BNCT treatment, where the infused agents are 95% isotopically enriched in 10B.
 ...
PMID:In vivo detection of a boron-neutron-capture agent in melanoma by proton observed 1H-10B double resonance. 796 38

A novel protocol for isotopically labeling bacterially expressed proteins is presented. This method circumvents problems related to poor cell growth, commonly associated with the use of minimal labeled media, and problems with protein induction encountered, less commonly, when using enriched labeled media. The method involves initially growing the bacterial cells to high optical density in a commercially available enriched labeled medium. Following a suitable growth period, the cells are transferred to a different (minimal) labeled medium, appropriate for induction. The method is demonstrated using the protein melanoma growth stimulating activity (MGSA).
J Biomol NMR 1994 May
PMID:A novel isotope labeling protocol for bacterially expressed proteins. 801 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>