Digital image analysis workflows for evaluation of cell behavior and tumor microenvironment to aid therapeutic assessment in high-risk neuroblastoma

Fecha de publicación: 01/09/2023 Fecha Ahead of Print: 01/08/2023

Autores de INCLIVA

Isaac Vieco Martí

Autor
Inmaculada Noguera Salvá

Autor
Maria Sanchez Sanchez

Autor
Samuel Navarro Fos

Autor
Rosa Noguera Salva

Autor

Participantes ajenos a INCLIVA

Stoks, M
Burgos-Panadero, R

Grupos y Plataformas de I+D+i

Grupo de Investigación Translacional de Tumores Sólidos Pediátricos

Leading Researcher

Samuel Navarro Fos

Abstract

Digital pathology and artificial intelligence are promising emerging tools in precision oncology as they provide more robust and reproducible analysis of histologic, morphologic and topologic characteristics of tumor cells and the surrounding microenvironment. This study aims to develop digital image analysis workflows for therapeutic assessment in preclinical in vivo models. For this purpose, we generated pipelines that enable automatic detection and quantification of vitronectin and & alpha;v & beta;3 in heterotopic high-risk neuroblastoma xenografts, demonstrating that digital analysis workflows can be used to provide robust detection of vitronectin secretion and & alpha;v & beta;3 expression by malignant neuroblasts and to evaluate the possibility of combining traditional chemotherapy (etoposide) with extracellular matrix-targeted therapies (cilengitide). Digital image analysis added evidence for the relevance of territorial vitronectin as a therapeutic target in neuroblastoma, since its expression is modified after treatment, with a mean percentage of 60.44% in combined therapy tumors vs 45.08% in control ones. In addition, the present study revealed the efficacy of cilengitide for reducing & alpha;v & beta;3 expression, with a mean & alpha;v & beta;3 positivity of 34.17% in cilengitide treated material vs 66.14% in control and with less tumor growth when combined with etoposide, with a final mean volume of 0.04 cm3 in combined therapy vs 1.45 cm3 in control. The results of this work highlight the importance of extracellular matrix-focused therapies in preclinical studies to improve therapeutic assessment for high-risk neuroblastoma patients.

Datos de la publicación

ISSN/ISSNe:: 0010-4825, 1879-0534
Tipo:: Article
Páginas:: 107364-107364
DOI:: 10.1016/j.compbiomed.2023.107364
PubMed:: 37598482

Documentos

Published Version

Métricas

Filiaciones

Vieco-Marti, I:: CIBER. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)

Instituto de Investigación. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)
Noguera, I:: CIBER. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)

Instituto de Investigación. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)
Sanchez-Sanchez, M:: CIBER. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)

Instituto de Investigación. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)
Navarro, S:: CIBER. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)

Instituto de Investigación. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)
Noguera, R:: CIBER. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)

Instituto de Investigación. Department of Pathology, Medical School, University of Valencia - INCLIVA Biomedical Health Research Institute, 46010, Valencia, Spain. CIBERONC, Carlos III Health Institute (Ministry of Economy and Competitive)