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)

An acid-stable transforming growth factor (TGF) that interacts with epidermal growth factor (EGF) receptors and is structurally related to EGF was isolated from serum-free culture fluids of Snyder-Theilen feline sarcoma virus-transformed rat embryo (FeSV-Fre) cells. Purification of this EGF-like TGF (eTGF) was achieved by molecular filtration chromatography and successive reverse-phase high pressure liquid chromatography steps on octadecyl support eluted with acetonitrile and 1-propanol gradients, respectively. Rat eTGF consists of a 7.4-kD single polypeptide chain that co-migrates with biological activity in dodecyl sulfate-polyacrylamide electrophoresis gels. Like preparations of a related TGF from human melanoma cells (Marquardt, H., and Todaro, G.J. (1982) J. Biol. Chem. 257, 5220-5225), but unlike EGF from rat, human, or mouse, rat eTGF has phenylalanine and lacks methionine. However, the sequence of the first 30 amino acid residues in rat eTGF is H2N-Val-Val-Ser-His-Phe-Asn-Lys-Cys-Pro-Asp-Ser-His-Thr-Gln-Tyr-Cys-Phe-His-Gly - Thr-(x)-Arg-Phe-Leu-Val-Gln-Glu-Glu-(Lys)-(Lys)-, which is significantly (20% and 28%) homologous to the NH2-terminal region of mouse EGF and human EGF, respectively. In addition to eTGF, molecular filtration chromatography of acid-soluble extracts from medium conditioned by FeSV-Fre cells resolved a 14-kD transforming factor(s) apparently devoid of intrinsic mitogenic activity but able to elicit a strong anchorage-independent growth response in the presence of eTGF or EGF. These results show that: 1) a 7.4-kDa TGF structurally and functionally related to EGF has been isolated from FeSV-Fre cells and 2) the full anchorage-independent growth-promoting activity of medium conditioned by FeSV-Fre cells is due to the coordinate action of at least two types of factors, the 7.4-kDa eTGF and a second 14-kDa transforming factor(s).
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PMID:Epidermal growth factor-like transforming growth factor. I. Isolation, chemical characterization, and potentiation by other transforming factors from feline sarcoma virus-transformed rat cells. 660 68

Ac-[Nle4, D-Phe7]-alpha-MSH4-11-NH2 an octapeptide, is a melanotropin analogue (Ac-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-NH2), which is a superpotent agonist of frog and lizard skin melanocytes and mouse S 91 (Cloudman) melanoma cells. This melanotropin possesses ultraprolonged activity on melanocytes, both in vitro and in vivo, and the peptide is resistant to inactivation by serum enzymes. The tritium-labeled congener was prepared by direct incorporation of [3H]-labeled norleucine into the peptide. The melanotropic activity of the labeled peptide is identical to the unlabeled analogue. This labeled peptide should be useful for studies on the localization and characterization of melanotropin receptors.
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PMID:Synthesis of tritium labeled Ac-[Nle4, D-Phe7]-alpha-MSH4-11-NH2: a superpotent melanotropin with prolonged biological activity. 660 41

Incubation of human Glu-plasminogen with 1,5-difluoro-2,4-dinitrobenzene leads to the specific intra-molecular cross-linking of the kringle 1+2+3 region and the light (B) chain region of plasminogen. This cross-link was found to prevent the conformational change which is induced in Glu-plasminogen by lysine analogues or by proteolytic removal of the NH2-terminal peptide. Our results suggest that the cross-link freezes the closed conformation of Glu-plasminogen, and it seems likely that the transition to the loose conformer requires separation of the kringle 1+2+3 region from the light (B) chain portion. The change in the relative position of these regions during the conformational change in plasminogen is also indicated by our observation that the rate of formation of the intramolecular cross-link is significantly decreased when transition to the loose conformer is induced either by saturation of the lysine-binding sites or by conversion to Lys-plasminogen. Cross-linked Glu-plasminogen is slowly activated by urokinase and melanoma tissue plasminogen activator, but in contrast with uncross-linked Glu-plasminogen conversion to Lys-plasminogen or saturation of lysine-binding sites with ligand does not increase the rate of activation because the cross-link prevents transition to the loose conformer which is susceptible to activation. The fibrin affinity of cross-linked Glu-plasminogen is practically identical with that of Glu-plasminogen. As in the case of uncross-linked Glu-plasminogen, removal of the NH2-terminal peptide causes a marked increase in fibrin affinity although the resulting cross-linked Lys-plasminogen is fixed in the closed conformation. This result suggests that the NH2-terminal peptide inhibits binding of plasminogen to fibrin by direct interaction with the fibrin-binding site, and the conformational change that normally accompanies its removal is not a prerequisite of strong binding.
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PMID:Importance of intramolecular interactions in the control of the fibrin affinity and activation of human plasminogen. 672 59

The antitumour selectivity of cisplatin and hydroxymalonatodiammine platinum II (Pt[OHmal(NH3)2]), a second generation platinum drug, was evaluated in C57B1/Cbi mice bearing advanced intramuscular B16 melanoma. At maximally tolerated doses, Pt[OHmal(NH3)2] produced greater inhibition of growth of the advanced B16 melanoma than did cisplatin. Comparison of dose-response curves for survival of B16 lung colony-forming cells and bone marrow stem cells treated in vivo indicated that selective killing of B16 cells was achieved with Pt[OHmal(NH3)2], whereas cisplatin was relatively nonselective. The extent of reaction of platinum with DNA at doses producing measurable levels of survival in tumour and marrow in vivo was similar to values previously observed in cultured cells treated with cisplatin in vitro. Studies of the amount of platinum bound to DNA in tumour and marrow following administration of the two drugs revealed that the improved selectivity of Pt[OHmal(NH3)2] was associated with a selective increase in the amount of platinum bound to tumour DNA, relative to cisplatin. In addition, platinum lesions produced in DNA by Pt[OHmal(NH3)2] appeared to be more effective in producing tumour cell killing than those produced by cisplatin. No significant excision of total DNA-bound platinum from tumour was observed up to 48 h after administration of either drug.
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PMID:Toxicity of cisplatin and hydroxymalonatodiammine platinum (II) towards mouse bone marrow and B16 melanoma in relation to DNA binding in vivo. 688 65

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

alpha-Melanocyte-stimulating hormone (alpha-MSH) is implicated in pigmentation, central nervous system and immune system functions, growth, mitogenesis, and melanoma. Evaluation of these roles has been hindered by the lack of alpha-MSH antagonists. A combinatorial chemistry-based diffusion assay is used to find random tripeptides that antagonize normal frog and human melanoma MSH receptors and to identify pharmacological groups responsible for receptor interaction. The alpha-MSH antagonist D-Trp-Arg-Leu-NH2 is used to demonstrate directly the contribution of MSH to normal skin tone in frogs following injection or topical application.
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PMID:Combinatorial diffusion assay used to identify topically active melanocyte-stimulating hormone receptor antagonists. 770 44

The three-dimensional solution structure of the growth-related protein-alpha/melanoma growth stimulatory activity (GRO/MGSA) has been solved by two-dimensional 1H nuclear magnetic resonance spectroscopy. The GRO/MGSA monomer consists of an NH2-terminal loop, a three-stranded antiparallel beta-sheet, and a COOH-terminal alpha-helix. Dimerization, which is apparent under the experimental conditions used (2 mM, pH 5.10, 30 degrees C), results in a six-stranded antiparallel beta-sheet and a pair of helices with 2-fold symmetry. While the basic fold is similar to that seen for interleukin-8 (IL-8) (Clore, G. M., Appella, E., Yamada, M., Matsushima, K., and Gronenborn, A. M. (1990) Biochemistry, 29, 1689-1696), there are differences in the ELR motif (residues 6-8), the turn involving residues 31-36, which is linked to the NH2-terminal region through the 9-35 disulfide bond. The most significant differences are in the NH2-terminal loop (residues 12-23). In IL-8, all the corresponding regions have been shown to be required for receptor binding (Clark-Lewis, I., Dewald, B., Loetscher, M., Moser, B., and Baggiolini, M. (1994) J. Biol. Chem. 269, 16075-16081). The structural differences thus have been identified between GRO/MGSA and IL-8 could contribute to their different receptor binding specificities.
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PMID:Solution structure of GRO/melanoma growth stimulatory activity determined by 1H NMR spectroscopy. 780 18

We have previously shown that mouse sarcoma 180 cells produce vascular endothelial growth factor [VEGF; Rosenthal et al., 1990, Growth Factors, 4: 53-59], an endothelial mitogen that stimulates angiogenesis. Recent reports have implicated metalloproteinases and their inhibitors in the regulation of vascular morphogenesis, tumor invasion, and metastasis. We report here that mouse sarcoma 180 cells produce two collagenase inhibitors. These inhibitors were purified by heparin-Sepharose affinity chromatography, gel filtration, and C4 reverse phase h.p.l.c. Analytical gel electrophoresis of the purified inhibitors (MS-22 and MS-31) revealed molecular masses of 22,000 and 31,000 Da under reducing conditions, and 20,000 and 30,000 Da under nonreducing conditions, respectively. The NH2-terminal amino acid sequence of MS-22 was identical to that of tissue inhibitor of metalloproteinases type 2 (TIMP-2) produced by human melanoma cells [Stetler-Stevenson et al., 1989, J. Biol. Chem. 264: 17374-17378) over the first 30 amino acids. The NH2-terminal amino acid sequence of MS-31 was identical to that of murine TIMP-1 [Gewert et al., 1989, EMBO J 6:651-657]. Statistical analysis of the amino acid composition data of these two mouse sarcoma 180-derived collagenase inhibitors confirms the identification of MS-22 as TIMP-2 and MS-31 as TIMP-1.
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PMID:Purification and characterization of two collagenase inhibitors from mouse sarcoma 180 conditioned medium. 780 96

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

This paper describes our efforts to study structure-activity relationships, improve the antimetastatic potency, and limit the in vivo enzymatic degradation of YIGSR-NH2, a synthetic peptide from the B1 chain of laminin, which reportedly has potential as an antimetastatic agent. To this end we have synthesized a series of psi (CH2NH) peptide analogs (5-9) of YIGSR-NH2 and a number of peptides in which the Tyr residue was replaced with D-Tyr (1), Phe (2), Phe (p-F) (3), and Phe(p-NH2) (4). All new peptides were assayed in vitro for their ability to promote cell attachment in both B16F10 mouse melanoma cells and HT-1080 human fibrosarcoma cells. On the basis of the in vitro assay results, peptides 3-5, 8, and 9 were tested in vivo for their ability to inhibit tumor metastasis to the lungs in mice that were coinjected in the tail vein with B16F10 melanoma cells and 1 mg of peptide. In summary, of the nine new peptides only the Phe(p-NH2) peptide 4 showed consistent in vitro cell attachment activity, but only low in vivo antimetastatic activity.
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PMID:Synthetic laminin-like peptides and pseudopeptides as potential antimetastatic agents. 793 66


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