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Interactions between emerging therapeutic targets and developmental pathways associated with tumorigenesis: emphasis on pediatric malignancies

Grant number: 14/20341-0
Support type:Research Projects - Thematic Grants
Duration: September 01, 2016 - August 31, 2021
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Luiz Gonzaga Tone
Grantee:Luiz Gonzaga Tone
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Carlos Alberto Scrideli ; Carlos Gilberto Carlotti Jr
Assoc. researchers: Ana Luiza Ongaro Seidinger Conte ; Edgard Eduard Engel ; Elvis Terci Valera ; Helio Rubens Machado ; Izilda Aparecida Cardinalli ; José Andrés Yunes ; Luciano Neder Serafini ; Paula Cristina dos Santos ; Ricardo Santos de Oliveira ; Silvia Regina Brandalise ; Simone dos Santos Aguiar ; Suely Kazue Nagahashi Marie ; Vitor Marcel Faça ; Wilson Araújo da Silva Junior
Associated scholarship(s):20/04850-2 - Technical support to assist in target validation, by analysis of molecular biology and silicon analysis, from results obtained for pediatric adrenocortical tumor (ACT); and support in the laboratory routine, BP.TT
17/26160-5 - Musashi-1 gene in medulloblastoma group 3 and 4, BP.DR
19/19772-0 - Technical support in laboratory routine and target validation through functional assays and molecular biology analysis, BP.TT
+ associated scholarships 18/23372-4 - Study of the effects of DNA demethylation on genes associated with developmental pathways in pediatric Ependymomas, BP.DR
19/00547-6 - Technical support in the laboratory routine and the search for new therapeutic targets using bioinformatics tools, BP.TT
18/04477-0 - Crosstalk signaling between TGF-beta and Wnt/beta-catenin pathways in Adrenocortical Tumors, BP.PD
18/05401-7 - "Demethylation of specific tumor suppressor in medulloblastoma using dCas9-Tet1 system", BP.PD
17/06511-8 - Investigation of Smad2/3-YAP complex as a chemoresistant factor in TP53, BP.PD
16/19820-6 - Investigation of new therapeutic targets from transcriptional networks of genes of the mitotic spindle associated with embryonic developmental pathways in the ependymoma: focus on molecular subgroups of worst outcome, BP.DR
16/19799-7 - Research therapeutic targets from gene expression networks of members of the TGF-b pathway associated with tumor progression of ependymomas of worse prognosis, BP.DR
16/23972-6 - Molecular classification of pediatric ependymomas, BP.MS
16/24117-2 - Notch signaling and the role of Notch/Skp2 axis in the tumorigenesis of Medulloblastoma, BP.PD - associated scholarships

Abstract

Currently, even with intensive multimodal treatment, 20% of children and adolescents with cancer will still die due to disease and over 40% of survivors develop sequelae that affect the adult quality of life. Therefore, more effective and safer treatment options for children with cancer are still needed to increase cure rates, decrease toxicity and to minimize the risk of long term effects on survivors. The biology of pediatric cancers are intrinsically associated with dysregulation of signaling pathways that control normal embryonic development. Among these pathways are Wnt, Shh and Notch, and TGF-², which also play an important role in carcinogenesis and are involved in tumor chemo-and radio-resistance. The study of these pathways in the context of the biology of pediatric tumors may constitute a new field for the identification of target genes and understanding of the long-term effects caused by the different treatment modalities of infant tumors. Thus, this project aims to identify co-expression networks associated with the transcriptional modules of the above mentioned pathways in different pediatric tumors (medulloblastoma, ependymoma, Ewing's sarcoma and adrenal carcinoma). From these data, genes considered plausible therapeutic targets (those previously studied by our group, those with therapeutic/prognostic value established in the literature or genes that have a promising scientific value for each studied tumor) will be validated and subsequently investigated in in vitro and in vivo models through different techniques. This research may provide new molecular perspectives, both to elucidate the specific mechanisms involved in pediatric tumor biology, as for the identification of new therapeutic strategies for treating this cohort. (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Leukemia drug shows the potential to treat aggressive pediatric brain cancer 
Leukemia drug shows the potential to treat aggressive pediatric brain cancer 
Novel technology developed to classify most common brain cancer in children 
Novel technology developed to classify most common brain cancer in children 
Articles published in other media outlets (87 total):
More itemsLess items
Estadão.com: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (30/Jun/2020)
UOL: Medicamento para leucemia pode tratar câncer cerebral infantil, diz estudo (30/Jun/2020)
UOL: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (18/Jun/2019)
Programa InfoSalud (Argentina): Un medicamento para la leucemia, con potencial para tratar un agresivo cáncer cerebral infantil (05/Aug/2020)
NCYT Amazings (Espanha): Un medicamento para la leucemia, con potencial para tratar un agresivo cáncer cerebral infantil (02/Aug/2020)
Al Día (Cuba): Un medicamento para la leucemia, con potencial para tratar un agresivo cáncer cerebral infantil (30/Jul/2020)
M3 India (Índia): Leukemia Drug Shows the Potential to Treat Aggressive Paediatric Brain Cancer (24/Jul/2020)
Mindzilla (Reino Unido): Leukemia Drug Shows the Potential to Treat Aggressive Paediatric Brain Cancer (23/Jul/2020)
Gazeta Shëndeti (Albânia): Leukemia drug shows the potential to treat aggressive pediatric brain cancer (23/Jul/2020)
Medical Xpress (Reino Unido): Leukemia drug shows the potential to treat aggressive pediatric brain cancer (22/Jul/2020)
Ecancer (Reino Unido): Leukaemia drug shows the potential to treat aggressive paediatric brain cancer (22/Jul/2020)
Medindia (Índia): Leukemia Drug Holds Promise in Treating Pediatric Brain Cancer (22/Jul/2020)
Brinkwire (Reino Unido): Leukemia drug shows the potential to treat aggressive pediatric brain cancer (22/Jul/2020)
All My Medicine: Leukemia drug shows the potential to treat aggressive pediatric brain cancer (22/Jul/2020)
The Science Times (EUA): Leukemia Treatment Can Potentially Treat Pediatric Brain Cancer (22/Jul/2020)
Gazeta Shëndeti (Albânia): Leukemia Drug Shows the Potential to Treat Aggressive Paediatric Brain Cancer (22/Jul/2020)
Thailand Medical News (Tailândia): Brain Cancer: Leukemia Drug Arsenic Trioxide Can Be Repurposed To Treat Aggressive Pediatric Brain Cancer (22/Jul/2020)
PharmaTutor (Índia): Leukemia drug shows the potential to treat aggressive pediatric brain cancer (22/Jul/2020)
Medical Dialogues (Índia): Leukemia drug may help treat aggressive pediatric brain cancer, finds study (22/Jul/2020)
Virginkillersweaterbuy: Leukemia Drug Shows the Potential to Treat Aggressive Paediatric Brain Cancer (22/Jul/2020)
NewsATW: Leukemia Drug Shows the Potential to Treat Aggressive Paediatric Brain Cancer (22/Jul/2020)
Bioengineer (Reino Unido): Leukemia drug shows the potential to treat aggressive pediatric brain câncer (21/Jul/2020)
Health Medicine Network (EUA): Leukemia drug shows the potential to treat aggressive pediatric brain câncer (21/Jul/2020)
Science Codex: Leukemia drug shows the potential to treat aggressive pediatric brain câncer (21/Jul/2020)
Life Extension Advocacy Foundation (EUA): Leukemia Drug Shows the Potential to Treat Aggressive Paediatric Brain Cancer (21/Jul/2020)
Life Extension Advocacy Foundation (EUA): Leukemia drug shows the potential to treat aggressive pediatric brain cancer (21/Jul/2020)
Scienmag Science Magazine (Reino Unido): Leukemia drug shows the potential to treat aggressive pediatric brain câncer (21/Jul/2020)
7thSpace: Leukemia drug shows the potential to treat aggressive pediatric brain câncer (21/Jul/2020)
Ariquemes : Remédio para leucemia tem chance para tratar câncer cerebral infantil (05/Jul/2020)
Jornal Cidade (Barreiras, BA) online: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (05/Jul/2020)
Mato Grosso Digital: Remédio para leucemia tem chance para tratar câncer cerebral infantil. (04/Jul/2020)
Biblioteca FMUSP: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (03/Jul/2020)
Jornal Joseense News: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (03/Jul/2020)
Coxim Agora: Remédio para leucemia tem chance para tratar câncer cerebral infantil (02/Jul/2020)
Instituto Oncoguia: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (02/Jul/2020)
ON Jornal: Remédio para leucemia tem chance para tratar câncer cerebral infantil (02/Jul/2020)
Portal do Governo do Estado de São Paulo: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (01/Jul/2020)
O Nortão online: Remédio para leucemia tem chance para tratar câncer cerebral infantil (01/Jul/2020)
Folha Nobre: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (01/Jul/2020)
Notícias ao Minuto: Remédio para leucemia tem chance para tratar câncer cerebral infantil (01/Jul/2020)
Notícias de Campinas: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (01/Jul/2020)
SBT Interior: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo - Jornal Imprensa Regional (01/Jul/2020)
Mix Vale: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (01/Jul/2020)
Terra: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (30/Jun/2020)
NE10: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (30/Jun/2020)
Jornal da Ciência online: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (30/Jun/2020)
Blog Jornal da Mulher: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (30/Jun/2020)
Ornan Serapião: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo - Jornal Imprensa Regional (30/Jun/2020)
Portal da Enfermagem: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (30/Jun/2020)
Jornal Integração: Pesquisadores descobrem medicamento para tratar câncer cerebral infantil (30/Jun/2020)
Central das Notícias: Medicamento para leucemia pode tratar câncer cerebral infantil, diz estudo (30/Jun/2020)
Central das Notícias: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (30/Jun/2020)
Programa InfoSalud (Argentina): Un medicamento para leucemia tiene potencial para tratar cáncer cerebral infantil agresivo (30/Jun/2020)
Medicina S/A: Plataforma barateia diagnóstico de tumor cerebral (28/Oct/2019)
LabNetwork: Método barateia diagnóstico de tumor cerebral em crianças e vira startup (21/Oct/2019)
Investe São Paulo: Método barateia diagnóstico de tumor cerebral em crianças e vira startup (18/Oct/2019)
NewsLab online: Método nacional otimiza técnicas de biologia molecular para baratear diagnóstico de câncer cerebral (18/Oct/2019)
Sociedade Científica: Método barateia diagnóstico de tumor cerebral em crianças e vira startup (18/Oct/2019)
Brasil CT&I: Método barateia diagnóstico de tumor cerebral em crianças e vira startup (18/Oct/2019)
Blog Saúde e Dicas: Bióloga do Piauí integra equipe de Nobel de Medicina: "Nunca desisti" (18/Oct/2019)
Rede Clipex: Método barateia diagnóstico de tumor cerebral em crianças e vira startup (17/Oct/2019)
Jornal da USP online: Método barateia diagnóstico de tumor cerebral em crianças e vira startup (17/Oct/2019)
Meio Norte online: Conheça piauiense que integra equipe do ganhador do Nobel de Medicina (12/Oct/2019)
USP Ribeirão Preto: Método barateia diagnóstico de tumor cerebral em crianças e vira startup (01/Oct/2019)
Science and Technology Research News (EUA): Novel Technology Developed to Classify Most Common Brain Cancer in Children (07/Aug/2019)
Al Día (Cuba): Nueva tecnología de bajo coste para la clasificación de los tumores cerebrales más comunes en niños (29/Jul/2019)
NCYT Amazings (Espanha): Nueva tecnología de bajo coste para la clasificación de los tumores cerebrales más comunes en niños (24/Jul/2019)
Maestroviejo (Espanha): Nueva tecnología de bajo coste para la clasificación de los tumores cerebrales más comunes en niños (24/Jul/2019)
Catalunya Vanguardista (Espanha): Tecnología bajo coste para tumores cerebrales en niños (24/Jul/2019)
SciDev.Net (Reino Unido): New method to classify brain tumour in children (27/Jun/2019)
SciDev.Net (América Latina e o Caribe): Nuevo método para clasificar tumor cerebral en niñez (25/Jun/2019)
Diário Potiguar: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (24/Jun/2019)
Diário Nacional: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (24/Jun/2019)
Bem Pra Você Oficial: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (24/Jun/2019)
Jornal Joseense News: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (20/Jun/2019)
Algomais online: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (19/Jun/2019)
Sociedade Científica: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (15/Jun/2019)
W Rádio Brasil: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (15/Jun/2019)
O Tempo online: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (14/Jun/2019)
Plantão News (MT): Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (14/Jun/2019)
Esteta : Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (14/Jun/2019)
Pampulha online: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (14/Jun/2019)
Jornal da Ciência online: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (14/Jun/2019)
Saúde em ação: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (14/Jun/2019)
Portal da Enfermagem: Nova tecnologia permite classificar o tumor cerebral mais comum em crianças (14/Jun/2019)
Jornal Imprensa Regional: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo - Jornal Imprensa Regional (02/Jul/2020)
Jornal de Brasília: Medicamento para leucemia tem potencial para tratar câncer cerebral infantil agressivo (30/Jun/2020)

Scientific publications (9)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DA SILVA FEITOSA, JOSE ANTONIO; DAS CHAGAS, PABLO FERREIRA; DE SOUSA, GRAZIELLA RIBEIRO; DE PAULA QUEIROZ, ROSANE GOMES; VEIGA CRUZEIRO, GUSTAVO ALENCASTRO; TONE, LUIZ GONZAGA; BORGES, KLEITON SILVA; VALERA, ELVIS TERCI. Frequency of theTP53p.R337H mutation in a Brazilian cohort of pediatric patients with solid tumors. MOLECULAR BIOLOGY REPORTS, v. 47, n. 8 JUL 2020. Web of Science Citations: 0.
DE ALMEIDA MAGALHAES, TACIANI; CRUZEIRO, GUSTAVO ALENCASTRO VEIGA; DE SOUSA, GRAZIELLA RIBEIRO; DA SILVA, KETERYNE RODRIGUES; LIRA, REGIA CAROLINE PEIXOTO; SCRIDELI, CARLOS ALBERTO; TONE, LUIZ GONZAGA; VALERA, ELVIS TERCI; BORGES, KLEITON SILVA. Notch pathway in ependymoma RELA-fused subgroup: upregulation and association with cancer stem cells markers expression. Cancer Gene Therapy, v. 27, n. 6, p. 509-512, JUN 2020. Web of Science Citations: 0.
DOS SANTOS KLINGER, PAULO HENRIQUE; ALBERICI DELSIN, LARA ELIS; VEIGA CRUZEIRO, GUSTAVO ALENCASTRO; ANDRADE, AUGUSTO FARIA; PEIXOTO LIRA, REGIA CAROLINE; DE ANDRADE, PAMELA VIANI; DAS CHAGAS, PABLO FERREIRA; DE PAULA QUEIROZ, ROSANE GOMES; TREVISAN, FELIPE AMSTALDEN; DE OLIVEIRA, RICARDO SANTOS; SCRIDELI, CARLOS ALBERTO; TONE, LUIZ GONZAGA; VALERA, ELVIS TERCI. Arsenic Trioxide exerts cytotoxic and radiosensitizing effects in pediatric Medulloblastoma cell lines of SHH Subgroup. SCIENTIFIC REPORTS, v. 10, n. 1 APR 22 2020. Web of Science Citations: 0.
MAGALHAES, TACIANI DE ALMEIDA; BORGES, KLEITON SILVA; DE SOUSA, GRAZIELLA RIBEIRO; BRANDALISE, SILVIA REGINA; SEIDINGER, ANA LUIZA; SCRIDELI, CARLOS ALBERTO; OBA-SHINJO, SUELI MIEKO; YUNES, JOSE ANDRES; TONE, LUIZ GONZAGA. The TP53 p.R337H mutation is uncommon in a Brazilian cohort of pediatric patients diagnosed with ependymoma. NEUROLOGICAL SCIENCES, v. 41, n. 3, p. 691-694, MAR 2020. Web of Science Citations: 0.
DAS CHAGAS, PABLO FERREIRA; BARONI, MIRELLA; BRASSESCO, MARIA SOL; TONE, LUIZ GONZAGA. Interplay between the RNA binding-protein Musashi and developmental signaling pathways. JOURNAL OF GENE MEDICINE, v. 22, n. 1 JAN 2020. Web of Science Citations: 0.
DE SOUSA, GRAZIELLA RIBEIRO; NAGAHASHI MARIE, SUELY KAZUE; OBA-SHINJO, SUELI MIEKO; ZAMBELLI RAMALHO, LEANDRA NAIRA; TONE, LUIZ GONZAGA; VALERA, ELVIS TERCI. A novel type of C11orf95-LOC-RELA fusion in a grade II supratentorial ependymoma: report of a case with literature review. CHILD'S NERVOUS SYSTEM, v. 35, n. 4, p. 689-694, APR 2019. Web of Science Citations: 0.
VEIGA CRUZEIRO, GUSTAVO ALENCASTRO; SALOMAO, KARINA BEZERRA; OLIVEIRA DE BIAGI, JR., CARLOS ALBERTO; BAUMGARTNER, MARTIN; STURM, DOMINIK; PEIXOTO LIRA, REGIA CAROLINE; MAGALHAES, TACIANI DE ALMEIDA; MILAN, MIRELLA BARONI; SILVEIRA, VANESSA DA SILVA; SAGGIORO, FABIANO PINTO; DE OLIVEIRA, RICARDO SANTOS; DOS SANTOS KLINGER, PAULO HENRIQUE; SEIDINGER, ANA LUIZA; YUNES, JOSE ANDRES; DE PAULA QUEIROZ, ROSANE GOMES; OBA-SHINJO, SUELI MIEKO; SCRIDELI, CARLOS ALBERTO; KAZUE NAGAHASHI, SUELY MARIE; TONE, LUIZ GONZAGA; VALERA, ELVIS TERCI. A simplified approach using Taqman low-density array for medulloblastoma subgrouping. ACTA NEUROPATHOLOGICA COMMUNICATIONS, v. 7, MAR 4 2019. Web of Science Citations: 0.
GERON, LENISA; SALOMAO, KARINA BEZERRA; BORGES, KLEITON SILVA; ANDRADE, AUGUSTO FARIA; PEREIRA CORREA, CAROLINA ALVES; SCRIDELI, CARLOS ALBERTO; TONE, LUIZ GONZAGA. Molecular characterization of Wnt pathway and function of -catenin overexpression in medulloblastoma cell lines. Cytotechnology, v. 70, n. 6, p. 1713-1722, DEC 2018. Web of Science Citations: 0.
SALOMAO, KARINA BEZERRA; VEIGA CRUZEIRO, GUSTAVO ALENCASTRO; BONFIM-SILVA, RICARDO; GERON, LENISA; RAMALHO, FERNANDO; SAGGIORO, FABIANO PINTO; SERAFINI, LUCIANO NEDER; ANTUNES MORENO, DANIEL; DE PAULA QUEIROZ, ROSANE GOMES; AGUIAR, SIMONE DOS SANTOS; CARDINALLI, IZILDA; YUNES, JOSE ANDRES; BRANDALISE, SILVIA REGINA; BRASSESCO, MARIA SOL; SCRIDELI, CARLOS ALBERTO; TONE, LUIZ GONZAGA. Reduced hydroxymethylation characterizes medulloblastoma while TET and IDH genes are differentially expressed within molecular subgroups. JOURNAL OF NEURO-ONCOLOGY, v. 139, n. 1, p. 33-42, AUG 2018. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.