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)

A 72-amino-acid chimeric protein, Chi1, was constructed from the N-terminal part of interleukin 8, IL-8-(1-53), and the C-terminal part of melanoma growth stimulatory activity, MGSA-(54-72). Chi1 protein showed receptor-binding specificity and biological activity similar, but not identical to IL-8 and decidedly different from MGSA. The structure of Chi1 was determined in solution by two-dimensional NMR and molecular-dynamics calculations. The structure resembled the structures of MGSA and IL-8 closely, containing a triple-stranded beta-sheet in the IL-8 part and an amphipathic alpha-helix in the MGSA part. Chi1 formed dimers at millimolar concentrations via the first strand from the N-terminus, analogous to IL-8 and MGSA. In contrast to the latter molecules, however, the alpha-helix of Chi1 did not pack against the beta-sheet part, but was an independent structural element. This structural difference could be explained mainly by the modulation of hydrophobic interactions between the helix and the rest of the protein in Chi1 as compared to IL-8 and MGSA. It is concluded that tight helix packing is not required for receptor binding and biological activity of Chi1.
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PMID:Structure and activity of a chimeric interleukin-8-melanoma-growth-stimulatory-activity protein. 863 39

A human melanoma cell line (MM96L) had a spontaneous mutation rate at the HGPRT locus of approx. 7 times normal. The cells had elevated dATP and dGTP pools, lacked purine nucleoside phosphorylase (PNP) and were sensitive to killing by deoxyadenosine, deoxyinosine and related purines but not to inosine or hypoxanthine. Four other melanoma cell lines exhibited a range of nucleoside sensitivities and dNTP pool sizes. Failure of intact MM96L cells to degrade exogenous deoxyadenosine and deoxyinosine to hypoxanthine was confirmed by NMR of culture medium. Normal melanocytes were PNP+ and were insensitive to deoxyinosine. Comparison of the metabolites of [14C]deoxyinosine from MM96L and a PNP+ cell line of similar doubling time (HeLa) showed that both cell types produced 14C-labelled guanine and adenine nucleotides, with [14C]dATP and [14C]dADP being found in MM96L. This indicates that human sAMP synthetase or a similar enzyme catalyses the conversion of dIMP to dAMP, the resultant elevation of dATP causing base misincorporation and a mutator phenotype.
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PMID:Purine deoxynucleoside metabolism in human melanoma cells with a high spontaneous mutation rate. 865 85

Interleukin-8 (IL-8), a CXC chemokine, is known to bring about chemotaxis and activation of neutrophils through high affinity binding to at least two distinct receptors, receptor-A and receptor-B. The IL-8 homolog melanoma growth stimulating activity (MGSA) is also active toward neutrophils. In contrast to IL-8, MGSA binds receptor-B with high affinity and binds receptor-A with approximately 400-fold lower affinity. Using the structure of IL-8 (Clore et al.(1990) Biochemistry, 29, 1689-1696; Baldwin et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 502-506) and the NMR-determined structure of MGSA (Fairbrother et al. (1994) J. Mol. Biol. 242, 252-270), we designed variants of both IL-8 and MGSA to investigate the basis of specificity for binding of these chemokines to the IL-8 receptors. The most outstanding structural difference between IL-8 and MGSA lies in the loop preceding the first beta-strand. When the corresponding (shorter) loop from MGSA was swapped into IL-8, both receptor-A and receptor-B binding affinities were significantly (>300-fold) reduced. However, with additional mutations that affect packing interactions, an IL-8 variant specific for receptor-B binding was produced. Conversely, when the same loop from IL-8 was swapped into MGSA, receptor-B binding was maintained with only a approximately 30-fold reduction in receptor-A affinity. Again, mutations affecting packing of the loop yielded a MGSA variant with high affinity for both receptors, like IL-8. Finally, we show, through point mutations in a monomeric IL-8 framework, that individual side chain substitutions can affect receptor specificity.
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PMID:Exchanging interleukin-8 and melanoma growth-stimulating activity receptor binding specificities. 866 82

The crude organic extract of Dendropanax arboreus was selected as a candidate for bioassayguided fractionation on the basis of its relatively selective cytotoxicity to a subset of cell lines within the National Cancer Institute's disease-oriented in vitro tumor-screening panel. The major compound responsible for the in vitro cytotoxicity was falcarinol (1). Several other known compounds were isolated and found to be cytotoxic, including dehydrofalcarinol (2), a diyenne (3), falcarindiol (4), and dehydrofalcarindiol (5). In addition, two novel polyacetylenes, dendroarboreols A (6) and B (7), were isolated and characterized by standard and inverse-detected NMR methods. Compounds were selected from this series for absolute stereochemical determination using the modified Mosher method and preliminary in vivo evaluation using a LOX melanoma mouse xenograft model.
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PMID:Cytotoxic falcarinol oxylipins from Dendropanax arboreus. 879 22

1H MR spectroscopy was used to correlate the metabolite signals in 66 untreated metastatic brain tumors with the results of Gd-DTPA enhanced MRI. Cubic volumes containing brain metastases of lung cancer (n = 17), mammary carcinoma (n = 24), melanoma (n = 12) and those originating from other tumors (n = 13) were examined using the double spin echo technique with CHESS pulses for water suppression and TE = 135 ms. Apart from trends toward reduced signals of choline-containing compounds (Cho) and reduced post-Gd MRI contrast in lung cancer compared with the other pathology groups, the four tumor groups had similar MRI and MRS characteristics. Metastases without lipid or lactate (Lact) signal in the 1H MR spectra were comparatively small in size with homogeneous post-Gd MRI enhancement (33 +/- 5%, means +/- SEM; n = 24) and elevated Cho signals compared with normal contralateral brain tissue (70 +/- 5% of contralateral N-acetyl aspartate signal; p < 0.001). The other metastases showed either unambiguous lipid signals (n = 30) or MRS detectable Lact (n = 12) and were heterogeneous on MRI with divergent signals of Gd-enhancement (49 +/- 5% vs 14 +/- 8%, p < 0.001) and Cho (88 +/- 10 vs 47 +/- 8% of contralateral NAA; p = 0.02). Those with Lact were significantly larger compared with both other groups (p < 0.02, both). It is concluded that brain metastases can be categorized into early stage (Cho), intermediate stage (lipid, higher Cho) and late stage metastases (Lact, lower Cho).
NMR Biomed 1996 Apr
PMID:1H MR spectroscopy detection of lipids and lactate in metastatic brain tumors. 888 70

A series of sulfonyl-N-hydroxyguanidine derivatives was designed and synthesized for cytotoxic evaluation as potential anticancer agents on the basis of the lead compound LY-181984. Replacement of the ureido moiety of the lead compound with hydroxyguanidine provided a stable cytotoxic agent. The conformation of sulfonyl-N-hydroxyguanidine derivatives, such as N-(4-chlorophenyl)-N'-[(benzo[2,1,3]thiadiazol-4-yl)sulfonyl]-N"- hydroxyguanidine (4g), investigated utilizing HMBC NMR, theoretical calculations, and X-ray crystallography, indicated stacking of the two aromatic rings. The derivatives were evaluated for in vitro cytoxicity against five human tumor cell lines, including HepG2, TSGH 8302, COLO 205, KB, and MOLT-4. The cytotoxic activities of the derived compounds against the human tumor cell lines were equal to or greater than that of the lead compound. N-(4-Chlorophenyl)-N'-[[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl]- N"- hydroxyguanidine (4n) and N-(4-chlorophenyl)-N'-[[3,5-dichloro-4-(2-chloro-4-nitrophenoxy)phenyl] sulfonyl]-N"-hydroxyguanidine (4o) exhibited the greatest growth inhibition of solid tumor cell lines. Compound 4o was found to possess antitumor activity against murine K1735/M2 melanoma xenografts.
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PMID:Synthesis and cytotoxic evaluation of substituted sulfonyl-N-hydroxyguanidine derivatives as potential antitumor agents. 921 47

Two new alkaloids, 9-carbethoxy-3-methylcarbazole and 9-formyl-3-methylcarbazole, and a known metabolite, 3-methyl-carbazole were isolated from the roots of Murraya koenigii. All three compounds were identified by detailed spectral analyses including 2D NMR studies and their structures confirmed by synthesis. Of the two new metabolites, the 9-formyl compound displayed weak cytotoxicity against both mouse melanoma B16 and adriamycin-resistant P388 mouse leukemia cell lines.
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PMID:Carbazole alkaloids from Murraya koenigii. 936 97

A new melanogenesis inhibitor, named amphistin, was isolated from the fermentation broth of an actinomycete strain KP-3052. Amphistin was purified from the culture filtrate by the combination of cation exchange, gel filtration, and aminosilyl silica gel chromatographic methods. The structure of amphistin was elucidated as gamma-(beta-histidinoalanino)homoalanine by NMR experiments including 1H-15N HMBC experiment and other spectroscopic analyses. Amphistin inhibited the melanogenesis of B16 melanoma cells at concentration of 6.8 microM.
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PMID:Amphistin, a new melanogenesis inhibitor, produced by an actinomycete. 940 84

A set of friedelane triterpenoids has been isolated from the stem bark exudates of Maytenus macrocarpa. It includes a new friedelan triterpene (1), together with the known compounds friedelin, 3-oxo-29-hydroxyfriedelane, 3-oxofriedelan-25-al, and canophyllol. The structures of these compounds were elucidated by spectroscopic and chemical evidence. Complete 1H and 13C assignments were achieved by 2D NMR spectroscopy. The new compound showed weak activity against aldose reductase. It did not display antitumor activity against P-388 lymphoid neoplasm, A-549 human lung carcinoma, HT-29 human colon carcinoma, or MEL-28 human melanoma cell lines.
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PMID:Friedelane triterpenoids from Maytenus macrocarpa. 946 56

Four known alkaloids, lycorine (1), 1,2-di-O-acetyllycorine (2), ambelline (3), and crinine (4) were isolated from the bulbs of Brunsvigia littoralis (Amaryllidaceae). 1H- and 13C-NMR spectra of 2 were completely assigned by means of 1D- and 2D-NMR techniques. The alkaloids (1-4) together with the synthesised 11-O-acetylambelline (3a) and 3-O-acetylcrinine (4a) were tested for antimalarial activity with two strains of cultured Plasmodium falciparum and for cytotoxicity with BL6 mouse melanoma cells. Structures 1 and 2 exhibited both antimalarial and cytotoxic activity.
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PMID:Cytotoxic and antimalarial alkaloids from Brunsvigia littoralis. 949 73


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