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 29-kDa monomeric dispase-digestive fragment of human plasma fibronectin has been purified by heparin affinity chromatography. The NH2-terminal sequence was determined as Ala1687-Val-Thr-Thr-Ile-Pro-Ala-Pro. By mass spectrometry the molecular weight was determined to be 30,241.9 with standard deviation of 3.9 amu. Therefore, we defined the C-terminal sequence of the 29-kDa fragment as Arg1957-Lys-Lys-Thr-Gly-Gln-Glu. This indicates that the fragment is composed of 277 amino acids. 125I-fibronectin and the 125I-labeled 29-kDa fragment bound to HL-60 (human acute promyelocytic leukemia) cells in a time-dependent, saturable, and reversible manner. Approximately 120 min was required to reach maximal binding. There were no differences in quantity or rate of binding of labeled fibronectin and 29-kDa fragment at temperatures of 4 degrees, 22 degrees, and 37 degrees C. The number of binding sites per HL-60 cell of fibronectin and the 29-kDa fragment were 140,000 with a Kd of 133 nM and 108,000 with a Kd of 250 nM, respectively. The binding of fibronectin to HL-60 cells was completely inhibited by this fragment, and by the peptides of RGDS and CS1 with IC50s of 3.6, 840, and 670 microM, respectively. Native fibronectin inhibited the direct binding of the 29-kDa fragment to HL-60 cells; however, RGDS peptide, peptide CS1, or two melanoma cell adhesion-promoting domain peptides in this 29-kDa fragment (peptide I; Tyr1906-Val1924, peptide II; Asp1946-Thr1960) did not block this binding. Neither heparitinase nor chondroitinase treatment of cells had any effect on these bindings. These results indicate that the C-terminal cell- and heparin-binding domain of fibronectin mediates HL-60 cell binding by direct interaction independently of RGD, CS1, and melanoma cell adhesion domains in this fragment.
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PMID:Binding site in human plasma fibronectin to HL-60 cells localizes in the C-terminal heparin-binding region independently of RGD and CS1. 769 49

In this study the relationship between tissue-type transglutaminase (TGase2) activity and the propensity to metastasize was investigated in human melanoma cell lines with different metastatic behavior. TGase2 catalyzes an acyl-transfer reaction between peptide-bound glutamine residues and primary amines, including the epsilon-amino group of lysine residues. Northern-blot analysis demonstrated that TGase2 RNA-expression (3.7 kb) was elevated in highly metastatic cell lines (MV3 and BLM) as compared to weakly metastatic ones (IF6 and 530). Immunoprecipitation and enzyme assays of TGase2 showed that the differential expression at the mRNA level was also reflected at the protein level. These findings reveal a positive relation between the expression of TGase2 and the metastatic properties of the human melanoma cell lines.
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PMID:Expression of tissue-type transglutaminase correlates positively with metastatic properties of human melanoma cell lines. 782 48

Mutations in N-ras exon 2 codon 61 were studied in formalin-fixed human melanoma metastases. DNA fragments including codon 61 were amplified by polymerase chain reaction (PCR) and mutational analysis was performed by oligonucleotide hybridization (ODN), allele specific PCR and PCR combined with single strand conformation polymorphism analysis (SSCP). Thirty metastases from 25 patients with 'spontaneous' cutaneous melanoma were compared with 35 metastases from 17 patients with 'hereditary' cutaneous melanoma. The frequency of mutations as measured by PCR/ODN was significantly higher in patients with hereditary melanoma (mutations in 24% versus 59%, p < 0.05). The most frequent mutations were C/A transversions to lysine (AAA). The occurrence of lysine mutations was, in addition, studied by allele specific polymerase chain reaction. Again, the mutation frequency was significantly higher in metastases from patients with hereditary melanoma. PCR/SSCP finally enabled the isolation of lysine mutant alleles and nucleotide sequence analysis which confirmed the presence of the mutated codon 61. The relatively higher frequency of N-ras mutations in tumours from patients with hereditary melanoma may be related to the hypermutability described in hereditary melanoma and dysplastic naevus syndrome. The results support an involvement of N-ras mutations in the molecular pathogenesis of melanoma.
Melanoma Res 1994 Jun
PMID:Melanoma metastases from patients with hereditary cutaneous malignant melanoma contain a high frequency of N-ras activating mutations. 791 62

We investigated the role of signal transduction systems in the attachment of human uveal melanoma cells to matrix proteins. Ocular melanoma cells established from primary tumours attached rapidly to all substrates examined. Preferred substrates of attachment were collagens type I, III and IV and fibronectin rather than laminin, gelatin, arginine-glycine-aspartine, vitronectin, poly-L-lysine or plastic. All cells showed rapid attachment to the preferred substrates (80% within 10 min). Manipulation of intracellular cyclic AMP or protein kinase C activity had relatively little effect on cell attachment. In contrast, attachment was significantly reduced by manipulating either intracellular calcium or calmodulin. After 15 min at 37 degrees C, the calcium ionophore ionomycin (5 microM) reduced attachment to 25%, and TMB8 (50 microM), which can reduce intracellular calcium, reduced attachment to 60%. The experimental calmodulin antagonist J8 (25 microM), a substituted naphthalene sulphonamide, reduced attachment to 40%. Similarly tamoxifen (25 microM), which has calmodulin antagonist activity in vitro, reduced attachment to 55%. Both J8 and tamoxifen inhibited cell attachment to a wide range of matrix proteins, suggesting that this effect on attachment is not dependent on the presence of specific adhesion receptors. Reduction of ocular melanoma tumour cell/matrix interactions through manipulation of intracellular calcium or calmodulin may therefore merit further investigation as a possible approach to reducing metastatic spread.
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PMID:Investigation of the role of signal transduction in attachment of ocular melanoma cells to matrix proteins: inhibition of attachment by calmodulin antagonists including tamoxifen. 792 90

Synthetic peptides related to amino acid residues 29-42 of human serum amyloid A (SAA), Tyr-Ile-Gly-Ser-Asp-Lys-Tyr-Phe-His-Ala-Arg-Gly-Asn-Tyr, were found to inhibit the adhesion of human T-lymphocytes and of mouse M4 melanoma cells to surfaces coated with the major cell adhesive glycoproteins of the extracellular matrix, laminin or fibronectin. Correspondingly inhibitory activity was manifested by the entire 14-residue peptide, by its YIGSD laminin-related domain, and by RGN, the fibronectin-related domain. Intact recombinant SAA (rSAA) and its 1-76 fragment, an amyloid A (AA) protein, also inhibited cell adhesion. The peptides did not inhibit collagen and ADP-induced aggregation of human platelets. Proteolysis of SAA by lysosomal enzymes originating from human neutrophils led to generation of specific peptide segments some of which pertain to the 29-42 domain. It is suggested that the acute-phase protein SAA might be involved, either directly or via its peptide fragments, in inhibition of inflammatory reactions or metastatic processes which depend on integrin and possibly other extracellular-matrix-specific receptors mediated specific recognition and interactions with immobilized components of blood-vessel walls.
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PMID:Inhibition of cell adhesion to glycoproteins of the extracellular matrix by peptides corresponding to serum amyloid A. Toward understanding the physiological role of an enigmatic protein. 803 6

A simple procedure has been developed for studying the transfer of DNA into cells using the process of receptor-mediated endocytosis. Poly-L-lysine 460 was covalently attached to the carbohydrate chains of avidin via periodate oxidation and NaBH4 reduction to give avidin-pLys460. Following purification through Sephacryl S-300, the conjugate was reacted with biotinylated transferrin. The resulting avidin-pLys460-[bio-transferrin] could be either fractionated by Superose 12 gel chromatography or used directly in experiments with DNA. Determination of the interaction between avidin-pLys460-]bio-transferrin] and DNA was carried out by nitro cellulose filter binding and agarose gel retardation assays. The conjugate was shown to bind DNA strongly, giving stable complexes soluble in 0.15-0.2 M salt solutions. Gene transfer using avidin-pLys460-[bio-transferrin] and the luciferase plasmid pRSVL was accomplished with Hela cells, alpha T3 pituitary cells and a human melanoma cell line used in the present study. Transfection was dependent on bio-transferrin and stimulated by the lysosomotropic agent chloroquine. The results are consistent with a receptor-mediated endocytosis mechanism of DNA delivery for Hela cells and a combination of receptor and adsorptive endocytosis for the alpha T3 pituitary and melanoma T-5 cell lines.
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PMID:Studies on the transfer of DNA into cells through use of avidin-polylysine conjugates complexed to biotinylated transferrin and DNA. 806 55

Six alpha-MSH(4-10) [Nle-Asp-His-D-Phe-Arg-Trp-Lys-amide] derivatives carrying 2 or 1 or no 2,3-dihydroxy-(2S)-propyl (DHP) groups on the Lys10 amino side chain were coupled to diethylene-triaminopentaacetic acid (DTPA, a chelator for 111In) in monomeric and dimeric forms and tested for their binding activity and bioactivity in vitro with mouse and human melanoma cell lines and by receptor autoradiography to tumor sections, as well as in vivo with normal and melanoma-bearing mice: DTPA-[Nle4,Asp5,D-Phe7,Lys(bis-DHP)10]-alpha-MSH(4-10),DTPA-[Nle4, Asp5, D-Phe7,Lys(mono-DHP)10]-alpha-MSH(4-10), DTPA[Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10), DTPA-bis-([Nle4,Asp5,D-Phe7,Lys(bis-DHP)10]-alpha-MSH(4-10)), DTPA-bis[([Nle4,Asp5,D-Phe7,Lys(mono-DHP)10]-alpha-MSH(4-10)) and DTPA-bis-([Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10)). In the receptor-binding assays with B16-F1 mouse and D10 human melanoma cells, the KD values ranged between 0.76 and 31.17 nM and in the melanin bioassay the results were similar (EC50 values between 0.15 and 4.40 nM). The tissue distribution of the 111In-labeled compounds in C57Bl/6J mice showed that the dimeric [111In]-DTPA-bis([Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10)) and the monomeric [111In]-DTPA-[Nle4,Asp5,D-Phe7,Lys(bis-DHP)10]-alpha-MSH(4-10) exhibited the lowest non-specific binding. In mice carrying B16-F1 melanoma tumors, the monomeric compound displayed 2-fold higher 111In uptake by the tumor and a much lower non-specific uptake by the liver (12-fold) and the kidneys (2.5-fold) than the dimeric derivative. This demonstrates that modification of the Lys10 side chain by DHP is a promising lead for new MSH radiopharmaceuticals for melanoma targeting.
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PMID:[111In]-DTPA-labeled analogues of alpha-melanocyte-stimulating hormone for melanoma targeting: receptor binding in vitro and in vivo. 807 62

Astrocytoma (WHO grade II, III), glioblastoma, malignant melanoma, and normal glial cell cultures, established from biopsies, were investigated by 1H MRS. At a 1H resonance frequency of 500 MHz (11.75 T) a high spectral resolution was achieved in 1D 1H spectra; in conjunction with 2D shift-correlated (COSY) MRS, resonances of alanine, aspartate, choline, creatine, glutamate, glutamine, hypotaurine, myo-inositol, phosphocreatine, phosphoryl-ethanolamine, phosphoryl-choline, lactate, lysine, N-acetylaspartate, taurine, threonine and valine could be identified. T1 relaxation times for the most prominent compounds are presented. T1 values of lactate ranged between 450 ms and 850 ms. The intensity of the lactate signal revealed differences between individual spectra, but exhibited no correlation between different tumor specimens or degree of malignancy. It was shown that the lactate signal at 1.3 ppm is covered by peaks arising from threonine and fatty acids. The choline signal level varied among spectra of different tumors, among tumors with similar degree of malignancy, and within the same tumor. Further preliminary differences due to aspartate, inositol and glutamine/glutamate were found in 1D and 2D COSY spectra between normal glial cells as well as different tumors. These results indicate that some differences observed in in vivo spectra may be attributable to secondary macroscopic structural changes (hypoxia, necrosis) and not to tumor inherent characteristics. Further correlation between in vivo and in vitro spectroscopy is therefore required.
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PMID:High-resolution one- and two-dimensional 1H MRS of human brain tumor and normal glial cells. 808 Jul 12

The antimetastatic effects of MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide (MDP), against three different types of highly metastatic murine tumour cells, B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 T lymphoma, were examined in C57BL/6, Balb/c and CDF1 mice, respectively. The administration of 100 micrograms of MDP-Lys(L18) 2 or 4 days before tumour inoculation led to a significant decrease in lung metastasis of B16-BL6 melanoma or colon 26-M3.1 carcinoma cells. MDP-Lys(L18) was also effective in the inhibition of liver metastasis of L5178Y-ML25 lymphoma cells by administration 2 or 4 days before tumour inoculation. The prophylactic effect of 100 micrograms of MDP-Lys(L18) on tumour metastasis was evident for the different administration routes, i.e. subcutaneous, intravenous or intranasal injection, or oral administration. It is of prime interest that oral administration of 1 mg of MDP-Lys(L18) induced a significant decrease in lung metastasis of B16-BL6 melanoma cells. Administration of MDP-Lys(L18) 4 days before assay led to induction of tumoricidal activity by peritoneal macrophages and growth inhibition by the sera against B16-BL6 or L929 cells. When MDP-Lys(L18) was subcutaneously administered five times after tumour inoculation to test therapeutic effect in an experimental and spontaneous metastasis model using B16-BL6 melanoma, the consecutive administrations of MDP-Lys(L18) significantly inhibited lung metastasis in tumour-bearing mice. These results suggest that MDP-Lys(L18) is able to enhance host resistance to reduce tumour metastasis and is a potent immunomodulating agent which may be applied prophylactically or therapeutically for the treatment of cancer metastasis.
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PMID:MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide, inhibits the metastasis of haematogenous and non-haematogenous tumours in mice. 814

Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these peptides, when present in cultures of lymphomononuclear cells from healthy donors or from cancer patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and (iii) an increase in cytotoxicity against K562, Daudi and HT-29 cells. Isolated monocytes responded also to those peptides with a release of IL-1 and TNF alpha and an increase of cytotoxicity against HT-29 cells. It was found that the active peptides had the following structural pattern: a length of at least 15 amino-acid residues with a proline at position 6, valine, leucine, isoleucine, glycine, alanine or lysine at position 2, and glutamic or aspartic acid at position 11. Replacement of Pro at position 6 with any other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those required for activity resulted in compounds with a marked decrease in the immunomodulating properties described, or lacking these properties altogether.
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PMID:Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus protein A. 814 92


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