New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X
Abstract 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 radia...
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Nature Publishing Group
2019-07-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-019-45799-4 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lorena Favaro Pavon David Capper Tatiana Tais Sibov Silvia Regina Caminada de Toledo Ulrich-W. Thomale Jean Gabriel de Souza Francisco Romero Cabral Carolina Maria Berra Marcos Devanir Silva da Costa Jardel Mendonça Niçacio Patrícia Alessandra Dastoli Daniela Mara de Oliveira Suzana M. F. Malheiros Edgar Ferreira da Cruz Jackeline Moraes Malheiros Sérgio Mascarenhas de Oliveira Nasjla Saba Silva Antonio Sérgio Petrilli Andrea Maria Cappellano Milena Colò Brunialti Reinaldo Salomão Manoel A. de Paiva Neto Ana Marisa Chudzinski-Tavassi Sérgio Cavalheiro |
spellingShingle |
Lorena Favaro Pavon David Capper Tatiana Tais Sibov Silvia Regina Caminada de Toledo Ulrich-W. Thomale Jean Gabriel de Souza Francisco Romero Cabral Carolina Maria Berra Marcos Devanir Silva da Costa Jardel Mendonça Niçacio Patrícia Alessandra Dastoli Daniela Mara de Oliveira Suzana M. F. Malheiros Edgar Ferreira da Cruz Jackeline Moraes Malheiros Sérgio Mascarenhas de Oliveira Nasjla Saba Silva Antonio Sérgio Petrilli Andrea Maria Cappellano Milena Colò Brunialti Reinaldo Salomão Manoel A. de Paiva Neto Ana Marisa Chudzinski-Tavassi Sérgio Cavalheiro New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X Scientific Reports |
author_facet |
Lorena Favaro Pavon David Capper Tatiana Tais Sibov Silvia Regina Caminada de Toledo Ulrich-W. Thomale Jean Gabriel de Souza Francisco Romero Cabral Carolina Maria Berra Marcos Devanir Silva da Costa Jardel Mendonça Niçacio Patrícia Alessandra Dastoli Daniela Mara de Oliveira Suzana M. F. Malheiros Edgar Ferreira da Cruz Jackeline Moraes Malheiros Sérgio Mascarenhas de Oliveira Nasjla Saba Silva Antonio Sérgio Petrilli Andrea Maria Cappellano Milena Colò Brunialti Reinaldo Salomão Manoel A. de Paiva Neto Ana Marisa Chudzinski-Tavassi Sérgio Cavalheiro |
author_sort |
Lorena Favaro Pavon |
title |
New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X |
title_short |
New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X |
title_full |
New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X |
title_fullStr |
New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X |
title_full_unstemmed |
New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X |
title_sort |
new therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a kunitz-type molecule, amblyomin-x |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2019-07-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1038/s41598-019-45799-4 |
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doaj-384af2c64a0143f7b07d35ffbf8a24082020-12-08T09:35:41ZengNature Publishing GroupScientific Reports2045-23222019-07-019111010.1038/s41598-019-45799-4New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-XLorena Favaro Pavon0David Capper1Tatiana Tais Sibov2Silvia Regina Caminada de Toledo3Ulrich-W. Thomale4Jean Gabriel de Souza5Francisco Romero Cabral6Carolina Maria Berra7Marcos Devanir Silva da Costa8Jardel Mendonça Niçacio9Patrícia Alessandra Dastoli10Daniela Mara de Oliveira11Suzana M. F. Malheiros12Edgar Ferreira da Cruz13Jackeline Moraes Malheiros14Sérgio Mascarenhas de Oliveira15Nasjla Saba Silva16Antonio Sérgio Petrilli17Andrea Maria Cappellano18Milena Colò Brunialti19Reinaldo Salomão20Manoel A. de Paiva Neto21Ana Marisa Chudzinski-Tavassi22Sérgio Cavalheiro23Discipline of Neurosurgery, Federal University of São PauloCharité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universitätzu Berlin, and Berlin Institute of Health, Department of NeuropathologyDiscipline of Neurosurgery, Federal University of São PauloPediatric Oncology Institute, Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC), Federal University of São PauloPediatric Neurosurgery, Campus Virchow Klinikum, Charité UniversitätsmedizinLaboratory of Molecular Biology, Butantan InstituteHospital Israelita Albert EinsteinDepartment of Pharmacology, Institute of Biomedical Science, University of São PauloDiscipline of Neurosurgery, Federal University of São PauloDiscipline of Neurosurgery, Federal University of São PauloDiscipline of Neurosurgery, Federal University of São PauloDepartment of Genetics and Morphology, University of BrasíliaDiscipline of Neurosurgery, Federal University of São PauloDiscipline of Nephrology, Federal University of São PauloCarlos Institute of Physics, São Paulo UniversityCarlos Institute of Physics, São Paulo UniversityPediatric Oncology Institute, Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC), Federal University of São PauloPediatric Oncology Institute, Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC), Federal University of São PauloPediatric Oncology Institute, Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC), Federal University of São PauloLaboratory of Immunology and Infectology, Federal University of São PauloLaboratory of Immunology and Infectology, Federal University of São PauloDiscipline of Neurosurgery, Federal University of São PauloLaboratory of Molecular Biology, Butantan InstituteDiscipline of Neurosurgery, Federal University of São PauloAbstract 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.https://doi.org/10.1038/s41598-019-45799-4 |