Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) is a reactive endogenous molecule with multiple functions and its cellular signaling activity is mainly mediated by activation of the soluble isoform of guanylyl cyclase, a heterodimeric (alpha/beta) hemeprotein. The expression of the NO-sensitive soluble isoform of guanylyl cyclase was studied in various cultured melanocytic cells by measuring the accumulation of guanosine 3',5'-cyclic monophosphate in the presence and absence of NO donors. Here we report that 3-morpholino-sydnonimine, a donor of NO redox species, and (Z)-1-[2- (2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, a direct NO donor, induced a 20-fold increase in intracellular guanosine 3',5'-cyclic monophosphate in nonmetastatic melanoma cells and normal melanocytes in culture that could be related to cellular melanin content in a concentration-dependent manner. The increased intracellular guanosine 3',5'-cyclic monophosphate was due to stimulation of the activity of soluble guanylyl cyclase as such increase was completely abolished by using a specific inhibitor of soluble guanylyl cyclase. The involvement of functional soluble guanylyl cyclase was further confirmed by the presence of alpha1 and beta1 subunits in these cells at both mRNA and protein levels. In contrast, none of the NO donors induced guanosine 3',5'-cyclic monophosphate production in metastatic melanoma cells, which could be attributed to the absence of the beta1 subunit that is essential for catalytic activity of the soluble isoform of guanylyl cyclase. Metastatic melanoma cells produced higher levels of intracellular guanosine 3',5'-cyclic monophosphate in response to natriuretic peptides than other cell types, however, due to upregulation of membrane-bound guanylyl cyclase activities, but they are less pigmented or unpigmented. The present finding suggests that NO signaling in association with melanogenesis is dependent on the soluble isoform of guanylyl cyclase, whereas absence of soluble guanylyl cyclase but the presence of membrane-bound guanylyl cyclase correlates with the metastatic behavior of melanoma cells.
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PMID:Differential expression of functional guanylyl cyclases in melanocytes: absence of nitric-oxide-sensitive isoform in metastatic cells. 1123 15

We identified 18 patients with the distinct clinical phenotype of susceptibility to disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis, and molds. This syndrome typically had its onset in adulthood (age range, 7-60 years; mean, 31.1 years; median, 32 years) and was characterized by profound circulating monocytopenia (mean, 13.3 cells/microL; median, 14.5 cells/microL), B lymphocytopenia (mean, 9.4 cells/microL; median, 4 cells/microL), and NK lymphocytopenia (mean, 16 cells/microL; median, 5.5 cells/microL). T lymphocytes were variably affected. Despite these peripheral cytopenias, all patients had macrophages and plasma cells at sites of inflammation and normal immunoglobulin levels. Ten of these patients developed 1 or more of the following malignancies: 9 myelodysplasia/leukemia, 1 vulvar carcinoma and metastatic melanoma, 1 cervical carcinoma, 1 Bowen disease of the vulva, and 1 multiple Epstein-Barr virus(+) leiomyosarcoma. Five patients developed pulmonary alveolar proteinosis without mutations in the granulocyte-macrophage colony-stimulating factor receptor or anti-granulocyte-macrophage colony-stimulating factor autoantibodies. Among these 18 patients, 5 families had 2 generations affected, suggesting autosomal dominant transmission as well as sporadic cases. This novel clinical syndrome links susceptibility to mycobacterial, viral, and fungal infections with malignancy and can be transmitted in an autosomal dominant pattern.
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PMID:Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. 2004 Jul 66

Vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase transmembrane receptor that has also a soluble isoform containing most of the extracellular ligand binding domain (sVEGFR-1). VEGF-A binds to both VEGFR-2 and VEGFR-1, whereas placenta growth factor (PlGF) interacts exclusively with VEGFR-1. In this study we generated an anti-VEGFR-1 mAb (D16F7) by immunizing BALB/C mice with a peptide that we had previously reported to inhibit angiogenesis and endothelial cell migration induced by PlGF. D16F7 did not affect binding of VEGF-A or PlGF to VEGFR-1, thus allowing sVEGFR-1 to act as decoy receptor for these growth factors, but it hampered receptor homodimerization and activation. D16F7 inhibited both the chemotactic response of human endothelial, myelomonocytic and melanoma cells to VEGFR-1 ligands and vasculogenic mimicry by tumor cells. Moreover, D16F7 exerted in vivo antiangiogenic effects in a matrigel plug assay. Importantly, D16F7 inhibited tumor growth and was well tolerated by B6D2F1 mice injected with syngeneic B16F10 melanoma cells. The antitumor effect was associated with melanoma cell apoptosis, vascular abnormalities and decrease of both monocyte/macrophage infiltration and myeloid progenitor mobilization. For all the above, D16F7 may be exploited in the therapy of metastatic melanoma and other tumors or pathological conditions involving VEGFR-1 activation.
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PMID:Antitumor activity of a novel anti-vascular endothelial growth factor receptor-1 monoclonal antibody that does not interfere with ligand binding. 2765 84