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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Autores principales: 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
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Publicado: Nature Portfolio 2019
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spelling oai:doaj.org-article:384af2c64a0143f7b07d35ffbf8a24082021-12-02T15:10:04ZNew therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X10.1038/s41598-019-45799-42045-2322https://doaj.org/article/384af2c64a0143f7b07d35ffbf8a24082019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-45799-4https://doaj.org/toc/2045-2322Abstract 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.Lorena Favaro PavonDavid CapperTatiana Tais SibovSilvia Regina Caminada de ToledoUlrich-W. ThomaleJean Gabriel de SouzaFrancisco Romero CabralCarolina Maria BerraMarcos Devanir Silva da CostaJardel Mendonça NiçacioPatrícia Alessandra DastoliDaniela Mara de OliveiraSuzana M. F. MalheirosEdgar Ferreira da CruzJackeline Moraes MalheirosSérgio Mascarenhas de OliveiraNasjla Saba SilvaAntonio Sérgio PetrilliAndrea Maria CappellanoMilena Colò BrunialtiReinaldo SalomãoManoel A. de Paiva NetoAna Marisa Chudzinski-TavassiSérgio CavalheiroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
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.
format article
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
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 Portfolio
publishDate 2019
url https://doaj.org/article/384af2c64a0143f7b07d35ffbf8a2408
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