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The chick chorioallantoic membrane model: A new in vivo tool to evaluate breast...

Pinto, MT; Ribeiro, AS; Conde, I; Carvalho, R; Paredes, J

The high plasticity of cancer stem-like cells (CSCs) allows them to differentiate and proliferate, specifically when xenotransplanted subcutaneously into immunocompromised mice. CSCs are highly tumorigenic, even when inoculated in small numbers. Thus, in vivo limiting dilution assays (LDA) in mice are the current gold standard method to evaluate CSC enrichment and activity. The chick embryo chorioallantoic memb...


Sympathetic activity in breast cancer and metastasis: partners in crime

Conceição, F; Sousa, DM; Paredes, J; Lamghari, M

The vast majority of patients with advanced breast cancer present skeletal complications that severely compromise their quality of life. Breast cancer cells are characterized by a strong tropism to the bone niche. After engraftment and colonization of bone, breast cancer cells interact with native bone cells to hinder the normal bone remodeling process and establish an osteolytic “metastatic vicious cycle”. The...


Cadherin expression and emt: A focus on gliomas

Noronha, C; Ribeiro, AS; Taipa, R; Castro, DS; Reis, J; Faria, C; Paredes, J

Cadherins are calcium-binding proteins with a pivotal role in cell adhesion and tissue homeostasis. The cadherin-dependent mechanisms of cell adhesion and migration are exploited by cancer cells, contributing to tumor invasiveness and dissemination. In particular, cadherin switch is a hallmark of epithelial to mesenchymal transition, a complex development process vastly described in the progression of most epit...


BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases th...

Dionísio, MR; Vieira, AF; Carvalho, R; Conde, I; Oliveira, M; Gomes, M; Pinto, MT; Pereira, P; Pimentel, J; Souza, C; Marques, MMC; Silva, VD

Brain metastases remain an unmet clinical need in breast oncology, being frequently found in HER2-overexpressing and triple-negative carcinomas. These tumors were reported to be highly cancer stem-like cell-enriched, suggesting that brain metastases probably arise by the seeding of cancer cells with stem features. Accordingly, we found that brain-tropic breast cancer cells show increased stem cell activity and ...


The crosstalk between cell adhesion and cancer metabolism

Sousa, B; Pereira, J; Paredes, J

Cancer cells preferentially use aerobic glycolysis over mitochondria oxidative phosphorylation for energy production, and this metabolic reprogramming is currently recognized as a hallmark of cancer. Oncogenic signaling frequently converges with this metabolic shift, increasing cancer cells’ ability to produce building blocks and energy, as well as to maintain redox homeostasis. Alterations in cell-cell and cel...


Pan-cancer association of a centrosome amplification gene expression signature ...

Almeida, B; Vieira, AF; Paredes, J; Bettencourt-Dias, M; Barbosa-Morais, N

Centrosome amplification (CA) is a common feature of human tumours and a promising target for cancer therapy. However, CA’s pan-cancer prevalence, molecular role in tumourigenesis and therapeutic value in the clinical setting are still largely unexplored. Here, we used a transcriptomic signature (CA20) to characterise the landscape of CA-associated gene expression in 9,721 tumours from The Cancer Genome Atlas (...


S100P is a molecular determinant of E-cadherin function in gastric cancer

Carneiro, P; Moreira, AM; Figueiredo, J; Barros, R; Oliveira, P; Fernandes, MS; Ferro, A; Almeida, R; Oliveira, C; Carneiro, F; Schmitt, F; Paredes, J

Background: E-cadherin has been awarded a key role in the aetiology of both sporadic and hereditary forms of gastric cancer. In this study, we aimed to identify molecular interactors that influence the expression and function of E-cadherin associated to cancer. Methods: A data mining approach was used to predict stomach-specific candidate genes, uncovering S100P as a key candidate. The role of S100P was evaluat...


SRC inhibition prevents P-cadherin mediated signaling and function in basal-lik...

Ribeiro, AS; Nobre, AR; Mendes, N; Almeida, J; Vieira, AF; Sousa, B; Carvalho, F; Monteiro, J; Polónia, A; Fonseca, M; Sanches, J; Santos, N; Seruca, R

BACKGROUND: Basal-like breast cancer (BLBC) is a poor prognosis subgroup of triple-negative carcinomas that still lack specific target therapies and accurate biomarkers for treatment selection. P-cadherin is frequently overexpressed in these tumors, promoting cell invasion, stem cell activity and tumorigenesis by the activation of Src-Family kinase (SRC) signaling. Therefore, our aim was to evaluate if the trea...


Mobile Magnetic Nanocatalysts for Bioorthogonal Targeted Cancer Therapy

Hoop, M; Ribeiro, AS; Rösch, D; Weinand, P; Mendes, N; Mushtaq, F; Chen, X; Shen, Y; Pujante, C; Puigmartí-Luis, J; Paredes, J; Nelson, B; Pêgo, AP

The use of magnetic nanorobots to activate chemotherapeutic prodrugs represents a promising alternative to current chemotherapeutic treatments. Here, a hybrid nanowire (NW) for targeted bioorthogonally driven activation of the latent chemotherapeutic prodrug 5-fluoro-1-propargyl-uracil (Pro-5-FU) in in vitro and in vivo cancer models is proposed. The NWs are composed of magnetic iron (Fe) and palladium (Pd), a ...


Geometric compensation applied to image analysis of cell populations with morph...

Figueiredo, J; Rodrigues, I; Ribeiro, J; Fernandes, MS; Melo, S; Sousa, B; Paredes, J; Seruca, R; Sanches, J

Immunofluorescence is the gold standard technique to determine the level and spatial distribution of fluorescent-tagged molecules. However, quantitative analysis of fluorescence microscopy images faces crucial challenges such as morphologic variability within cells. In this work, we developed an analytical strategy to deal with cell shape and size variability that is based on an elastic geometric alignment algo...


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