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)

Patients receiving high-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT) may experience life-threatening hemorrhagic myocarditis. The authors investigated whether HDC was associated with an acquired platelet defect. Platelet aggregation and release were evaluated after HDC in ten patients with either metastatic breast carcinoma or melanoma. Platelets underwent shape change and a primary wave of aggregation. High-dose chemotherapy was associated with the inhibition of secondary aggregation of platelets induced by adenosine diphosphate (ADP), arachidonic acid, prostaglandin H2 (PGH2) analog (U44619), and collagen. Although electron microscopic study of the platelets revealed normal morphologic features with an adequate number of dense bodies and alpha-granules, release of adenosine triphosphate (ATP) from dense granules was less than 20% of normal. The acquired platelet defect occurred before development of thrombocytopenia. Aggregation of platelets from normal volunteers was not inhibited by either the addition of the chemotherapeutic agents, chemotherapy metabolites, or the patients' sera. In conclusion, HDC induces an acquired abnormality in platelet secretion and aggregation which may contribute to the development of hemorrhagic complications after ABMT.
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PMID:Platelets acquire a secretion defect after high-dose chemotherapy. 231 53

Transduction of signals initiating motility by extracellular matrix (ECM) molecules differed depending on the type of matrix molecule and whether the ligand was in solution or bound to a substratum. Laminin, fibronectin, and type IV collagen stimulated both chemotaxis and haptotaxis of the A2058 human melanoma cell line. Peak chemotactic responses were reached at 50-200 nM for laminin, 50-100 nM for fibronectin, and 200-370 nM for type IV collagen. Checkerboard analysis of each attractant in solution demonstrated a predominantly directional (chemotactic) response, with a minor chemokinetic component. The cells also migrated in a concentration-dependent manner to insoluble step gradients of substratum-bound attractant (haptotaxis). The haptotactic responses reached maximal levels at coating concentrations of 20 nM for laminin and type IV collagen, and from 30 to 45 nM for fibronectin. Pretreatment of cells with the protein synthesis inhibitor, cycloheximide (5 micrograms/ml), resulted in a 5-30% inhibition of both chemotactic and haptotactic responses to each matrix protein, indicating that de novo protein synthesis was not required for a significant motility response. Pretreatment of cells with 50-500 micrograms/ml of synthetic peptides containing the fibronectin cell-recognition sequence GRGDS resulted in a concentration-dependent inhibition of fibronectin-mediated chemotaxis and haptotaxis (70-80% inhibition compared to control motility); negative control peptide GRGES had only a minimal effect. Neither GRGDS nor GRGES significantly inhibited motility to laminin or type IV collagen. Therefore, these results support a role for the RGD-directed integrin receptor in both types of motility response to fibronectin. After pretreatment with pertussis toxin (PT), chemotactic responses to laminin, fibronectin, and type IV collagen were distinctly different. Chemotaxis to laminin was intermediate in sensitivity; chemotaxis to fibronectin was completely insensitive; and chemotaxis to type IV collagen was profoundly inhibited by PT. In marked contrast to the inhibition of chemotaxis, the hepatotactic responses to all three ligands were unaffected by any of the tested concentrations of PT. High concentrations of cholera toxin (CT; 10 micrograms/ml) or the cAMP analogue, 8-Br-cAMP (0.5 mM), did not significantly affect chemotactic or haptotactic motility to any of the attractant proteins, ruling out the involvement of cAMP in the biochemical pathway initiating motility in these cells. The sensitivity of chemotaxis induced by laminin and type IV collagen, but not fibronectin, to PT indicates the involvement of a PT-sensitive G protein in transduction of the signals initiating motility to soluble laminin and type IV collagen.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Signal transduction for chemotaxis and haptotaxis by matrix molecules in tumor cells. 232

We have investigated the effects of sulfated chitin derivatives and heparin on the invasion of B16-BL6 melanoma cells through reconstituted basement membrane Matrigel which contains laminin, type IV collagen, heparin sulfate proteoglycan, and entactin. 6-O-sulfated chitin (S-chitin) and 6-O-sulfated and carboxymethyl chitin (SCM-chitin) significantly inhibited the penetration of tumor cells through Matrigel in parallel with the increased degree of sulfation. However, 6-O- and N-sulfated but partially N-deacetylated chitin derivative (SCM-chitosan) and CM-chitin had no effect. SCM-chitin with a high degree of sulfation (SCM-chitin III), which exhibited fairly low levels of anticoagulant activity, was more effective than intact heparin. SCM-chitin III and heparin were also shown to block the attachment and migration of tumor cells to laminin-coated substrates, which are considered to be involved in tumor invasion. The inhibition of cell attachment and migration by SCM-chitin III and heparin is likely to depend upon their specific binding to laminin molecules (possibly the heparin-binding domain). Degradation of heparan sulfate by heparanase was inhibited by SCM-chitin III and heparin in a dose-dependent manner. Surprisingly, SCM-chitin III could inhibit type IV collagenolytic activity of tumor cells more potently than heparin. Thus, nontoxic SCM-chitin III of low anticoagulant properties may provide a promising basis for the prevention of cancer metastasis.
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PMID:Inhibition by sulfated chitin derivatives of invasion through extracellular matrix and enzymatic degradation by metastatic melanoma cells. 234 May 12

The short-term effects of ethanol (85.4, 170.8, and 256.2 mM) on cellular viability, proliferation, migration, and invasion were investigated on murine melanoma cells. Experiments with the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene indicated that the two highest concentrations of ethanol induced low microviscosity (high lipid fluidity). Cellular viability and proliferation, as determined by the incorporation of [3H]IdUR, were unaffected by all three concentrations of ethanol. A membrane migration assay and a collagen type IV invasion assay evaluated cellular migration and invasion, respectively. For B16F10 and K1735 cells, the migration rate was significantly increased by 170.8 and 256.2 mM concentrations of ethanol. Although the invasion of B16F10 cells was not affected, invasion of K1735 cells was inhibited by 170.8 and 256.2 mM ethanol. The effect of ethanol on the cytoskeleton was monitored by fluorescent staining of F-actin. In contrast to untreated cells, F-actin staining of 256.2 mM ethanol-treated cells showed spike-like projections from the cell surface. Our findings suggest that ethanol can influence cell migration and invasion in vitro, as well as F-actin organization.
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PMID:The influence of ethanol on cell membrane fluidity, migration, and invasion of murine melanoma cells. 234 77

The adhesion and motility of tumor cells on basement membranes is a central consideration in tumor cell invasion and metastasis. Basement membrane type IV collagen directly promotes the adhesion and migration of various tumor cell types in vitro. Our previous studies demonstrated that tumor cells adhered and spread on surfaces coated with intact type IV collagen or either of the two major enzymatically purified domains of this protein. Only one of these major domains, the pepsin-generated major triple helical fragment, also supported tumor cell motility in vitro, implicating the involvement of the major triple helical region in type IV collagen-mediated tumor cell invasion in vivo. The present studies extend our previous observations using a synthetic peptide approach. A peptide, designated IV-H1, was derived from a continuous collagenous region of the major triple helical domain of the human alpha 1(IV) chain. This peptide, which has the sequence GVKGDKGNPGWPGAP, directly supported the adhesion, spreading, and motility of the highly metastatic K1735 M4 murine melanoma cell line, as well as the adhesion and spreading of other cell types, in a concentration-dependent manner in vitro. Furthermore, excess soluble peptide IV-H1, or polyclonal antibodies directed against peptide IV-H1, inhibited type IV collagen-mediated melanoma cell adhesion, spreading, and motility, but had no effect on these cellular responses to type I collagen. The full complement of cell adhesion, spreading, and motility promoting activities was dependent upon the preservation of the three prolyl residues in the peptide IV-H1 sequence. These studies indicate that peptide IV-H1 represents a cell-specific adhesion, spreading, and motility promoting domain that is active within the type IV collagen molecule.
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PMID:Characterization of a synthetic peptide from type IV collagen that promotes melanoma cell adhesion, spreading, and motility. 236 34

A resin histological and ultrastructural study of 9 fibrotic extraocular muscles from 2 patients who underwent enucleation because of advanced intraocular malignant melanoma is reported. Total fibrosis of the extraocular muscles was evident in one case and extensive fibrosis in the other case. The patients did not suffer from congenital fibrosis syndrome. Ultrastructurally, the muscle tissue was replaced by collagen fibrils showing great variability of caliber.
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PMID:Massive fibrosis of extraocular muscles related to intraocular tumor. 236 83

As the first step in developing an in vitro model of melanoma cells infiltrating the dermis, B16 murine melanoma cells were cultured on and in type I collagen gels. Under these conditions, the melanoma cell adopted an elongated or dendritic form. Cell proliferation was suppressed in the culture system using the collagen gel as compared with the conventional monolayer culture on plastic. Microcinematographically, this suppression was found to be due to an extension of the cell cycle time of each individual cell. On the other hand, there were no appreciable differences in proliferation pattern between the cells cultured on type I and IV collagen film and those cultured on plastic. These results suggest that there are interactions between type I collagen in the gel form and melanoma cells, especially with respect to cell growth.
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PMID:Proliferative potential of murine melanoma cells cultured in or on collagen gel. 238 Apr 34

Expression of intermediate filament (IF) isotypes was studied in six human and two murine melanoma cell lines. With one exception, these lines expressed IFs only of the vimentin type; neurofilament peptides, desmin and GFAP were not detected. However, the M5 human melanoma line also expressed extensive cytokeratin tonofilament arrays, as visualized by immunofluorescence with a panel of eleven monoclonal antibodies and hetero-antisera to cytokeratins; only the keratin 19-specific antibody BA16 did not react. By 2 D gel electrophoresis, five major keratin peptides were detected (keratins 7, 8, 13, 17 and 18), and an additional 57 kD peptide was detected on immunoblots with several antikeratin antibodies. Also observed in M5 cells was focal collapse of tonofilament arrays in mitotic cells. All the melanoma lines tested were positive for S100; M5 and two other cell lines were also positive for the 220-240 kD neuroectoderm-associated cell-surface differentiation antigen defined by monoclonal antibody UJ 127:11. In all the melanoma cell lines, secretion of extracellular matrix proteins (fibronectin, laminin and collagen type IV) was sparse or absent, and all were negative for the epithelial cell markers HMG-1 and HMG-2. Co-expression of keratin and vimentin by a melanoma cell line is discussed in the light of recent controversy concerning expression of cytokeratins by other neoplasms of putative neuroectodermal origins.
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PMID:Phenotypic analysis of cultured melanoma cells. Expression of cytokeratin-type intermediate filaments by the M5 human melanoma cell line. 242 48

The effects of retinol, all-trans-retinoic acid, isotretinoin and etretinate on the activity of basement membrane collagen degrading enzyme was studied in melanoma cells. The results indicated that retinoids at concentrations of up to 10(-6) M did not significantly affect type IV collagenolytic activity in these cells in vitro. Since type IV collagenolytic enzyme may be involved in the metastatic potential of tumour cells, it appears that retinoids do not affect the metastatic potential of melanoma cells by affecting type IV collagenolytic activity.
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PMID:Effects of retinoids on type IV collagenolytic activity in melanoma cells. 243 Apr 9

Human umbilical vein endothelial cells express a heterodimeric adhesion receptor complex consisting of noncovalently associated alpha and beta subunits that under reducing conditions have molecular masses of 135 kDa and 115 kDa, respectively. This complex can be isolated in pure form from an affinity matrix consisting of an Arg-Gly-Asp-containing heptapeptide and is specifically immunoprecipitated with monoclonal antibodies (mAbs) directed against the vitronectin receptor of human melanoma cells. These data suggest that this complex is one member of a large family of cell adhesion receptors. One of the mAbs, LM609, inhibits the attachment of human endothelial cells to fibrinogen, von Willebrand factor, and vitronectin yet has no effect on the attachment of these cells to fibronectin, collagen, or laminin. In addition, mAb LM609 inhibits attachment of endothelial cells to an immobilized synthetic peptide containing the Arg-Gly-Asp sequence. This adhesion receptor appears structurally similar to the IIb/IIIa glycoprotein complex expressed on platelets yet is antigenically distinct, since mAb LM609 fails to recognize IIb/IIIa glycoproteins. This receptor organizes in clusters on endothelial cells during their attachment to von Willebrand factor, vitronectin, or the Arg-Gly-Asp-containing heptapeptide. The data presented in this report suggest that Arg-Gly-Asp recognition may play a significant role in biological events associated with vascular proliferation.
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PMID:Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. 244 58


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