Histopathological profiling of pediatric synovial sarcoma PDX (Patient-Derived Xenograft) samples and the establishment of spheroid (3D) cell culture."

• Grant number: 23/14392-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Larissa Akemi Kido de Barros
• Grantee: Larissa de Abreu Fernandes
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil

Abstract

Childhood cancer is a group of diseases with its own characteristics in terms of histopathology and clinical behavior, corresponding to between 1% and 4% of all malignant tumors in most populations aged 0 to 19. Synovial sarcoma (SS) is one of the types of tumors that affects children and adolescents and is considered the most common non-rhabdomyosarcoma soft tissue tumor in this age group. In the childhood cancer context, precision medicine stands out as a promising approach that aims to find more effective and less toxic therapies, considering the specific characteristics of each patient. To achieve this goal, research has focused on in vivo models, such as patient-derived xenograft models (PDX), and in vitro models, such as three-dimensional (3D) cell culture. However, despite the advantages of these techniques in reproducing the tumor environment, it is necessary to standardize them for application in translational studies. Thus, this study aims to characterize and validate synovial sarcoma PDX samples through histopathological analysis and to establish the culture of spheroids from these xenotransplanted samples. SS samples xenograft-derived in immunosuppressed mice (n=7), previously collected, will be processed, and evaluated for histological pattern, compared with the slides of primary samples from the patients and between the different generations of PDX. Moreover, an immunohistochemical technique will be carried out to validate the PDXs using SS diagnostic markers. For the standardization of the spheroids, SS samples derived from PDXs that better recreate morphologically the primary tumors (n=3) will be used for tests to create the 3D model. These tests include the physical and enzymatic dissociation of tumors, cell counting, cell viability testing and photographic recording.