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Nucleolin Overexpression Predicts Patient Prognosis While Providing a Framework...

Fernandes, Ângela Valério; Fonseca, Nuno A.; Gonçalves, Nélio; Cruz, Ana F.; Pereira, Marta I.; Gregório, Ana C.; Moura, Vera; Ladeirinha, Ana F.

Notwithstanding the advances in the treatment of lung cancer with immune checkpoint inhibitors, the high percentage of non-responders supports the development of novel anticancer treatments. Herein, the expression of the onco-target nucleolin in patient-derived pulmonary carcinomas was characterized, along with the assessment of its potential as a therapeutic target. The clinical prognostic value of nucleolin f...


Cell surface Nucleolin represents a novel cellular target for neuroblastoma the...

Brignole, Chiara; Bensa, Veronica; Fonseca, Nuno A.; Del Zotto, Genny; Bruno, Silvia; Cruz, Ana F.; Malaguti, Fabiana; Carlini, Barbara; Morandi, Fabio

Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Nucleolin (NCL) is a protein overexpressed and partially localized on the cell surface of tumor cells of adult cancers. Little is known about NCL and pediatric tumors and nothing is reported about cell surface NCL and NB. Methods: NB cell lines, Schwannian stroma-poor NB tumors and bone marrow (BM)-infilt...


The Enhanced Efficacy of Intracellular Delivery of Doxorubicin/C6-Ceramide Comb...

Cruz, Ana F.; Caleiras, Mariana B.; Fonseca, Nuno A.; Gonçalves, Nélio; Mendes, Vera M.; Sampaio, Susana F.; Moura, Vera; Melo, Joana B.

Targeting multiple cellular populations is of high therapeutic relevance for the tackling of solid tumors heterogeneity. Herein, the ability of pegylated and pH-sensitive liposomes, functionalized with the nucleolin-binding F3 peptide and containing doxorubicin (DXR)/C6-ceramide synergistic combination, to target, in vitro, ovarian cancer, including ovarian cancer stem cells (CSC), was assessed. The underlying ...


GMP-grade nanoparticle targeted to nucleolin downregulates tumor molecular sign...

Fonseca, Nuno A.; Gregório, Ana C.; Mendes, Vera M.; Lopes, Rui; Abreu, Teresa; Gonçalves, Nélio; Manadas, Bruno; Lacerda, Manuela; Figueiredo, Paulo

Patients with breast or ovarian cancer have not benefited from improved efficacy with pegylated liposomal doxorubicin relative to free drug, likely due to the limited extent of the enhanced permeability and retention (EPR) effect, further compromising drug bioavailability in the tumor. Herein it is hypothesized that targeting nucleolin overexpressed in tumor endothelial cells (readily accessible from the vascul...


Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel ...

Romano, Sofia; Moura, Vera; Simões, Sérgio; Moreira, João Nuno; Gonçalves, João

Nucleolin arises as a relevant target for cancer therapy, as it is overexpressed at the surface of cancer and angiogenic endothelial cells thus enabling a dual cellular targeting strategy. Immunotherapeutic strategies, albeit of proven therapeutic relevance, have been scarcely explored against this target. Therefore, this work aimed at engineering an anti-nucleolin VHH-based antibody capable of triggering antic...


Inoculated cell density as a determinant factor of the growth dynamics and meta...

Gregório, Ana C.; Fonseca, Nuno A.; Moura, Vera; Lacerda, Manuela; Figueiredo, Paulo; Simões, Sérgio; Dias, Sérgio; Moreira, João Nuno

Copyright: © 2016 Gregório et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.; 4T1 metastatic breast cancer model have been widely used to study stage IV human breast cancer. However, the frequent inoculation of a large nu...


Inoculated Cell Density as a Determinant Factor of the Growth Dynamics and Meta...

Gregório, Ana C.; Fonseca, Nuno A.; Moura, Vera; Lacerda, Manuela; Figueiredo, Paulo; Simões, Sérgio; Dias, Sérgio; Moreira, João Nuno

4T1 metastatic breast cancer model have been widely used to study stage IV human breast cancer. However, the frequent inoculation of a large number of cells, gives rise to fast growing tumors, as well as to a surprisingly low metastatic take rate. The present work aimed at establishing the conditions enabling high metastatic take rate of the triple-negative murine 4T1 syngeneic breast cancer model. An 87% 4T1 t...


Towards a siRNA-containing nanoparticle targeted to breast cancer cells and the...

Gomes-da-Silva, Lígia C.; Santos, Adriana O.; Bimbo, Luís M.; Moura, Vera; Ramalho, José S.; Lima, Maria C. Pedroso de; Simões, Sérgio; Moreira, João N.

The present work aimed at designing a lipid-based nanocarrier for siRNA delivery towards two cell sub-populations within breast tumors, the cancer and the endothelial cells from angiogenic tumor blood vessels. To achieve such goal, the F3 peptide, which is specifically internalized by nucleolin overexpressed on both those sub-populations, was used as a targeting moiety. The developed F3-targeted stable nucleic ...


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