New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X

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Pavon, Lorena Favaro ^[1] ; Capper, David ^{[2, 3, 4, 5, 6]} ; Sibov, Tatiana Tais ^[1] ; Caminada de Toledo, Silvia Regina ^[7] ; Thomale, Ulrich-W. ^[8] ; de Souza, Jean Gabriel ^{[9, 10]} ; Cabral, Francisco Romero ^[11] ; Berra, Carolina Maria ^[12] ; Silva da Costa, Marcos Devanir ^{[1, 7]} ; Nicacio, Jardel Mendonca ^{[1, 7]} ; Dastoli, Patricia Alessandra ^{[1, 7]} ; de Oliveira, Daniela Mara ^[13] ; Malheiros, Suzana M. F. ^{[11, 1]} ; da Cruz, Edgar Ferreira ^[14] ; Malheiros, Jackeline Moraes ^[15] ; de Oliveira, Sergio Mascarenhas ^[15] ; Silva, Nasjla Saba ^[7] ; Petrilli, Antonio Sergio ^[7] ; Cappellano, Andrea Maria ^[7] ; Brunialti, Milena Colo ^[16] ; Salomao, Reinaldo ^[16] ; de Paiva Neto, Manoel A. ^[1] ; Chudzinski-Tavassi, Ana Marisa ^{[9, 10]} ; Cavalheiro, Sergio ^{[1, 7]}

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^[1] Univ Fed Sao Paulo, Discipline Neurosurg, Sao Paulo, SP - Brazil

^[2] Charite Univ Med Berlin, Berlin - Germany

^[3] Free Univ Berlin, Berlin - Germany

^[4] Humboldt Univ, Berlin - Germany

^[5] Berlin Inst Hlth, Dept Neuropathol, Berlin - Germany

^[6] German Canc Res Ctr, Partner Site Berlin, German Canc Consortium DKTK, Heidelberg - Germany

^[7] Univ Fed Sao Paulo, Pediat Oncol Inst, Grp Apoio Ao Adolescente & Crianca Com Canc GRAAC, Sao Paulo, SP - Brazil

^[8] Charite, Campus Virchow Klinikum, Pediat Neurosurg, Berlin - Germany

^[9] Butantan Inst, Lab Mol Biol, Sao Paulo, SP - Brazil

^[10] Butantan Inst, Ctr Excellence New Target Discovery CENTD, Sao Paulo, SP - Brazil

^[11] Hosp Israelita Albert Einstein, Sao Paulo, SP - Brazil

^[12] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo, SP - Brazil

^[13] Univ Brasilia, Dept Genet & Morphol, Brasilia, DF - Brazil

^[14] Univ Fed Sao Paulo, Discipline Nephrol, Sao Paulo, SP - Brazil

^[15] Univ Sao Paulo, Carlos Inst Phys, Sao Carlos, SP - Brazil

^[16] Univ Fed Sao Paulo, Lab Immunol & Infectol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, JUL 10 2019.
• Citações Web of Science: 0

Resumo

EPNs comprise a heterogeneous group of neuroepithelial tumors, accounting for about 10% of all intracranial tumors in children and up to 30% of brain tumors in those younger than 3 years. Actually, the pattern therapy for low-grade EPNs includes complete surgical resection followed by radiation therapy. Total surgical excision is often not possible due to tumor location. The aim of this study was to evaluate, for the first time, the anti-tumor activity of Amblyomin-X in 4 primary cultures derived from pediatric anaplastic posterior fossa EPN, Group A (anaplastic, WHO grade III) and one primary culture of a high grade neuroepithelial tumor with MN1 alteration, which was initially misdiagnosed as EPN: i) by in vitro assays: comparisons of temozolomide and cisplatin; ii) by intracranial xenograft model. Amblyomin-X was able to induce cell death in EPN cells in a more significant percentage compared to cisplatin. The cytotoxic effects of Amblyomin-X were not detected on hFSCs used as control, as opposed to cisplatin-treatment, which promoted a substantial effect in the hAFSCs viability. TEM analysis showed ultrastructural alterations related to the process of cell death: mitochondrial degeneration, autophagosomes and aggregate-like structures. MRI and histopathological analyzes demonstrated significant tumor mass regression. Our results suggest that Amblyomin-X has a selective effect on tumor cells by inducing apoptotic cell death and may be a therapeutic option for Group AEPNs. (AU)

• Processo FAPESP: 12/06944-8 - Efeito do Amblyomin-X na interface do sistema imune e hemostático durante a progressão do tumor RENCA ( carcinoma renal murino): in vivo e in vitro
• Beneficiário: Jean Gabriel de Souza
• Modalidade de apoio: Bolsas no Brasil - Doutorado