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Vieco-Marti, I.

Publications and source records attributed to Vieco-Marti, I..

2 recordsLinked to original sources

DANEELpath: Open-source Digital analysis tools for histopathological research. Applications in NEuroblastoma modELs

Despite the considerable expansion of bioimage analysis as a subfield of biomedical sciences, there is an ongoing need for comprehensive image analysis pipelines to address specific biological inquiries. In the tumor microenvironment, the extracellular matrix (ECM) plays a pivotal role in cancer progression, promoting tumor cell adaptability, intratumor heterogeneity, and therapeutic resistance. In neuroblastoma (NB), the ECM glycoprotein vitronectin (VN) has been associated with more aggressive tumors. Three-dimensional (3D) hydrogels are an emerging biomimetic tool with significant potential for studying the role of ECM elements and testing new mechano-drugs such as cilengitide (CLG), a potential therapeutic agent to treat high-risk (HR) NB due to its ability to inhibit VN activity in cells. To gain a more detailed understanding of the effects of VN and CLG in 3D-grown NB cells, we developed DANEELpath, an open-source image analysis toolkit. DANEELpath integrates deep learning techniques, specific segmentation of individual and cluster cells through mathematical morphology pipelines, and extraction of spatial features within whole-slide images. Thanks to its versatility, DANEELpath is adaptable to address different biological questions and has significant potential for use in a variety of research fields and model systems, which could help advance biomedical discovery.

cancer biology↗

Vitronectin binding affinity and cell viability effect of novel mechanotherapy drugs for neuroblastoma

High-risk neuroblastoma (HR-NB) is an aggressive form of childhood cancer with a five-year survival rate of under 50%, underscoring the need for more efficacious and less toxic treatments. The glycoprotein Vitronectin (VN) has been linked to poor prognosis in patients with HR-NB, and thus inhibitors of its function represent a promising avenue for molecular mechanotherapy. The present study sought to investigate the binding affinity between the somatomedin B (SMB) domain of VN and natural compounds derived from medicinal plants. The therapeutic potential of -amyrin (AMY), lupeol (LUP), and Olax chalcone A (Olax CHA) was tested in combination with an integrin antagonist of VN, cilengitide (CLG), using the SK-N-BE(2) HR-NB cell line as a model. Molecular docking studies indicated a potential for protein-ligand interactions for all selected compounds, of which CLG demonstrated the most favorable binding free energy (kcal/mol), followed by LUP, AMY and Olax CHA. Molecular dynamics simulations demonstrated that the SMB domain of VN initially exhibited flexibility, with alpha carbon-root mean square deviation (RMSD) stabilizing at approximately 1.8-2.1 [A]. While all compounds demonstrated a dose-dependent decrease in SK-N-BE(2) cell viability, CLG exhibited higher IC50 values. Although the combination of AMY and LUP with CLG did not result in enhanced efficacy, Olax CHA exhibited a superior antiproliferative effect with higher IC50 values than AMY and LUP, and additionally showed potential synergism with CLG, suggesting a more effective therapeutic approach. This work provides valuable insights into the potential use of mechanotherapy drugs and natural products to enhance HR-NB treatment that can be expanded in future studies centered on Olax CHA.

cancer biology↗