Dados do Trabalho

Título

ESTABLISHMENT AND CHARACTERIZATION OF IN VITRO AND IN VIVO MODELS OF GROUP A POSTERIOR FOSSA EPENDYMOMA AND THERAPEUTIC EVALUATION OF 5-FLUOROURACIL

Introdução

Ependymoma (EPM) is a neoplasm that originates from ependymal cells, being the third most common among pediatric cancers affecting the Central Nervous System (CNS). Among the subtypes of Posterior Fossa (PF) EPM, Group A is the one with the worst prognosis. Treatment for patients includes surgery and adjuvant radiotherapy, with a significant portion of patients experiencing recurrence and ultimately resulting in fatality.

Objetivo

Establish and characterize in vitro and in vivo models of Group A posterior fossa ependymoma and evaluate the therapeutic effects of 5-fluorouracil.

Métodos

For the establishment of preclinical models of EPM in vitro and in vivo, patients are selected with a clinical history of CNS tumor suggestive of EPM and requiring surgical treatment for tumor removal. After obtaining Informed Consent or Assent, the tumor sample is collected at the surgical center of the Barretos Children’s Cancer Hospital. Tumors collected from patients are used for the establishment of primary culture (2D and 3D), followed by Short Tandem Repeats (STR) analysis for genetic compatibility assessment. The samples are also used to generate Patient-Derived Xenograft (PDX) models, both orthotopic and heterotopic, in NSG or NU/J mice. Tumors collected from animals are evaluated for histopathological and immunohistochemical similarities with the primary patient sample. Once the models are established, the effect of 5-FU on the treatment of primary EPM cultures will be investigated, and the results validated in the PDX models.

Resultados

With the tumor samples collected from patients, our research group previously established primary cell lines named HCB562, HCB591, and HCB596, along with their respective PDX models identified as OXP-2, OXP24, and OP29. Among the primary cultures of PF EPM, HCB591 showed the best response in cell proliferation and clonogenic capacity assays. As for the PDX models, the collected tumors were evaluated for histopathology, which indicated high mitotic activity, increased cell proliferation and angiogenesis, as well as the presence of areas of hemorrhage and necrosis, similar to the characteristics observed in patient samples. The results described so far highlight the significance of the generated model for therapeutic evaluation and for confirming the effect of 5-FU in treating this type of tumor. The project was approved by the CEP: protocol number 6.134.758, and by the CEUA: protocol number 014/2021, both from the Barretos Cancer Hospital.

Conclusões

The similarities observed in the tumors generated in the PDX models, compared to the primary patient samples, underscore the significance of the generated models for the scientific community. The in vitro and in vivo models enhance our understanding of tumor biology and provide opportunities for conducting tests with drug panels for novel therapeutic approaches. We hope that in the future, these models can contribute to the identification of personalized treatments for EPM.

Palavras-chave

Posterior Fossa Ependymoma
PDX
Personalized Therapy

Financiador do resumo

MPT; Barretos Cancer Hospital; Case No. 13/2021