Biology subjects

Noguera, R.

Publications and source records attributed to Noguera, R..

4 recordsLinked to original sources

bioRxiv2025

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↗

bioRxiv2025

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↗

bioRxiv2023

MOXD1 is a gate-keeper of organ homeostasis and functions as a tumor-suppressor in neuroblastoma

Neuroblastoma is a childhood cancer believed to result from dysfunctional development. Its origin during embryogenesis remains poorly understood. The lack of appropriate models has hindered in-depth mapping of tumor-driving events. Here, we identify a novel tumor-suppressor gene that predicts poor survival in high-risk disease, by applying bulk and single cell RNA sequencing data of neuroblastoma and human fetal adrenal glands. Trunk neural crest-specific MOXD1 discriminates cell populations during normal and tumor development, with implications for deciphering neuroblastoma cell origin. We created an embryonic conditional knockout model and show that cell type-specific loss of MOXD1 leads to disrupted organ homeostasis and failed adrenal gland formation, home for neuroblastoma. We show that MOXD1 is a tumor suppressor gene in zebrafish, chick, and mice in vivo models. One-Sentence SummaryNeural crest-specific MOXD1 is a de novo tumor-suppressor gene in childhood cancers arising during embryogenesis.

cancer biology↗

bioRxiv2018

Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients

In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of non-invasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in two independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis and overall survival, revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential expression analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume, suggesting this miRNA signature may be applied to monitor disease burden.

cancer biology↗