Refined high-content imaging-based phenotypic drug screening in zebrafish xenografts

Sturtzel, Caterina (avtor), Zajec, Živa (avtor), Dernovšek, Jaka (avtor), Tomašič, Tihomir (avtor), Taschner-Mandl, Sabine (avtor), Distel, Martin (avtor)

Zebrafish xenotransplantation models are increasingly applied for phenotypic drug screening to identify small compounds for precision oncology. Larval zebrafish xenografts offer the opportunity to perform drug screens at high-throughput in a complex in vivo environment. However, the full potential of the larval zebrafish xenograft model has not yet been realized and several steps of the drug screening workflow still await automation to increase throughput. Here, we present a robust workflow for drug screening in zebrafish xenografts using high-content imaging. We established embedding methods for high-content imaging of xenografts in 96-well format over consecutive days. In addition, we provide strategies for automated imaging and analysis of zebrafish xenografts including automated tumor cell detection and tumor size analysis over time. We also compared commonly used injection sites and cell labeling dyes and show specific site requirements for tumor cells from different entities. We demonstrate that our setup allows us to investigate proliferation and response to small compounds in several zebrafish xenografts ranging from pediatric sarcomas and neuroblastoma to glioblastoma and leukemia. This fast and cost-efficient assay enables the quantification of anti-tumor efficacy of small compounds in large cohorts of a vertebrate model system in vivo. Our assay may aid in prioritizing compounds or compound combinations for further preclinical and clinical investigations.

• Jezik: Angleški jezik
• Ključne besede: cancer models, phenotypic screening
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: 16 str.
• Številčenje: Vol. 7, art. 44
• PID: 20.500.12556/RUL-146346-31b66c38-f629-0ade-335e-3ea531c9b90b
• UDK: 615.4:54:616-006
• ISSN pri članku: 2397-768X
• DOI: 10.1038/s41698-023-00386-9
• COBISS.SI-ID: 153170179
• Datum objave v RUL: 24.05.2023

Gradivo je del revije

• Naslov: npj precision oncology
• Skrajšan naslov: npj precis. oncol.
• Založnik: Springer Nature, University of Minnesota, The Hormel Institute
• ISSN: 2397-768X
• COBISS.SI-ID: 526771225

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: fenotipski pregled, cebrica, tumorske celice, presajanje zdravil, ksenografti celic, onkologija, farmacevtska kemija, tumorji