Patient-Derived Tumor Xenografts Plus Ex Vivo Models Enable Drug Validation for Tenosynovial Giant Cell Tumors.
Ann Surg Oncol
; 28(11): 6453-6463, 2021 Oct.
Article
em En
| MEDLINE
| ID: mdl-33748895
ABSTRACT
INTRODUCTION:
Tenosynovial giant cell tumor (TGCT) is a locally aggressive tumor with colony-stimulating factor 1 receptor (CSF1R) signal expression. However, there is a lack of better in vivo and ex vivo models for TGCT. This study aims to establish a favorable preclinical translational platform, which would enable the validation of efficient and personalized therapeutic candidates for TGCT. PATIENTS ANDMETHODS:
Histological analyses were performed for the included patients. Fresh TGCT tumors were collected and sliced into 1.0-3.0 mm3 sections using a sterilized razor blade. The tumor grafts were surgically implanted into subrenal capsules of athymic mice to establish patient-derived tumor xenograft (PDTX) mouse models. Histological and response patterns to CSF1R inhibitors evaluations were analyzed. In addition, ex vivo cultures of patient-derived explants (PDEs) with endpoint analysis were used to validate TGCT graft response patterns to CSF1R inhibitors.RESULTS:
The TGCT tumor grafts that were implanted into athymic mice subrenal capsules maintained their original morphological and histological features. The "take" rate of this model was 95% (19/20). Administration of CSF1R inhibitors (PLX3397, and a novel candidate, WXFL11420306) to TGCT-PDTX mice was shown to reduce tumor size while inducing intratumoral apoptosis. In addition, the CSF1R inhibitors suppressed circulating nonspecific monocyte levels and CD163-positive cells within tumors. These response patterns of engrafts to PDTX were validated by ex vivo PDE cultures.CONCLUSIONS:
Subrenal capsule supports the growth of TGCT tumor grafts, maintaining their original morphology and histology. This TGCT-PDTX model plus ex vivo explant cultures is a potential preclinical translational platform for locally aggressive tumors, such as TGCT.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
/
Tumor de Células Gigantes de Bainha Tendinosa
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Ann Surg Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China