Navegando por Palavras-chave "Fgf2"

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    Blocking fgf2 with a new specific monoclonal antibody impairs angiogenesis and experimental metastatic melanoma, suggesting a potential role in adjuvant settings
    (Elsevier ireland ltd, 2016) de Aguiar, Rodrigo Barbosa [UNIFESP]; Parise, Carolina Bellini [UNIFESP]; Teixeira Souza, Carolina Rosal; Braggion, Camila [UNIFESP]; Quintilio, Wagner; Moro, Ana Maria; Navarro Marques, Fabio Luiz; Buchpiguel, Carlos Alberto; Chammas, Roger; de Moraes, Jane Zveiter [UNIFESP]
    Compelling evidence suggests that fibroblast growth factor 2 (FGF2), overexpressed in melanomas, plays an important role in tumor growth, angiogenesis and metastasis. In this study, we evaluated the therapeutic use of a new anti-FGF2 monoclonal antibody (mAb), 3F12E7, using for that the B16-F10 melanoma model. The FGF2 neutralizing effect of this antibody was certified by in vitro assays, which allowed the further track of its possible in vivo application. 3F12E7 mAb could be retained in B16-F10 tumors, as shown by antibody low-pH elution and nuclear medicine studies, and also led to reduction in number and size of metastatic foci in lungs, when treatment starts one day after intravenous injection of B16-F10 cells. Such data were accompanied by decreased CD34(+) tumor vascular density and impaired subcutaneous tumor outgrowth. Treatments starting one week after melanoma cell intravenous injection did not reduce tumor burden, remaining the therapeutic effectiveness restricted to early-adopted regimens. Altogether, the presented anti-FGF2 3F12E7 mAb stands as a promising agent to treat metastatic melanoma tumors in adjuvant settings. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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    Caracterização In Vitro Do Anticorpo Monoclonal Anti-Fgf2 3F12E7 São Paulo 2016
    (Universidade Federal de São Paulo (UNIFESP), 2017-01-31) Braggion, Camila [UNIFESP]; Moraes, Jane Zveiter De [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The aim of the present study was to characterize the in vitro action of the anti-FGF2 3F12E7 monoclonal antibody (mAb), which showed relevant activity in vivo, reducing tumor vascular density and inhibiting B16F10 melanoma metastasis. We started ana-lyzing the tube formation in matrigel, using human umbilical vein endothelial cells (HUVECs), in the presence or absence of 3F12E7 mAb. The results showed signifi-cant inhibition of the process. By immunoenzymatic and immunofluorescence as-says, it was observed that 3F12E7 mAb binds specifically to HUVECs. It has been found that 3F12E7 mAb inhibited the binding of FGF2 to HUVEC and that anti-FGF2 receptors (FGFR1 and FGFR2) and anti-sindecan-4 interfered with the binding of 3F12E7 mAb to those cells. It was further noted that 3F12E7 mAb interfered in the MAPK signaling pathway by inhibition of the extracellular signal regulated protein ki-nase (phosphorylated ERK), and that such inhibition was specific and increased with-in the first hour of cell treatment. The PI3K signaling pathway, however, does not ap-pear to be influenced by the presence of 3F12E7 mAb, since no significant change in the nitric oxide concentration in the cell culture supernatants was observed. Taken together, the results presented herein suggest that the therapeutic effects of 3F12E7 mAb, observed in vivo, may be due to the inhibition of FGF2 intracellular signaling. The presence of 3F12E7 mAb in the tumor microenvironment seems to prevent the binding of FGF2 to its receptors and, consequently, the formation of the ternary com-plex, responsible for many activities of the angiogenic agent. In addition, our results support the idea of 3F12E7 mAb therapeutic value and still show its potential as a useful tool in tumor microenvironment studies.