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Molecular e functional characterization of bone and soft tissue sarcomas of children and adolescents

Grant number: 11/10459-5
Support type:Regular Research Grants
Duration: September 01, 2011 - August 31, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Silvia Regina Caminada de Toledo
Grantee:Silvia Regina Caminada de Toledo
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Antonio Sergio Petrilli ; Carla Renata Pacheco Donato Macedo ; Indhira Dias Oliveira ; Maria Teresa de Seixas Alves ; Simone de Campos Vieira Abib


Sarcomas are a heterogeneous group of malignant tumors with a high frequency in children. From a genetic standpoint, sarcomas can be divided into two main groups, which are distinguishable by cytogenetic findings. One group is characterized by the presence of simple karyotypes, near diploid, with a few specific chromosomal changes, which include the rhabdomyosarcoma (RMS), Ewing's sarcoma (ES) and synovial sarcoma (SS). The second group presents complex karyotypes with a high degree of genomic instability, in which it characterizes osteosarcoma (OS). Although chemotherapeutic agents and surgical techniques vary with the type of cancer and location of disease, sarcomas, bone and soft tissue share a common characteristic: the survival curves for these diseases remain stagnant in the last two decades, despite the numerous clinical protocols and various agents used. The objective of this study will be the evaluation of the expression profile of fusion and development genes in RMS, SE and SS, and the role of MAPK7 gene in OS. RT-PCR, qPCR will be performed to analyze the fusion genes: PAX3-FKHR, PAX7-FKHR, EWS-FLI1, SYT-SSX1, SYT-SSX2 and development genes: IGF2, IHH, GLI1 and PTCH1 in RMS, SE and SS tumors. In OS evaluate if the increased expression of the MAPK7 gene, observed in a previous study, is results from a mutation of this gene by sequencing. It will be performed MAPK7 gene silencing and later we will carry out technical viability, proliferation, apoptosis, migration and invasion in silenced and not silenced OS cells, so that we can elucidate the role of MAPK7 gene as a possible prognostic marker in OS. (AU)

Scientific publications
(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)
SILVA LOPES, LUANA JOYCE; TESSER-GAMBA, FRANCINE; PETRILLI, ANTONIO SERGIO; DE SEIXAS ALVES, MARIA TERESA; GARCIA-FILHO, REYNALDO JESUS; CAMINADA TOLEDO, SILVIA REGINA. MAPK pathways regulation by DUSP1 in the development of osteosarcoma: Potential markers and therapeutic targets. Molecular Carcinogenesis, v. 56, n. 6, p. 1630-1641, JUN 2017. Web of Science Citations: 8.
TESSER-GAMBA, FRANCINE; DA SILVA LOPES, LUANA JOYCE; PETRILLI, ANTONIO SERGIO; CAMINADA TOLEDO, SILVIA REGINA. MAPK7 Gene Controls Proliferation, Migration and Cell Invasion in Osteosarcoma. Molecular Carcinogenesis, v. 55, n. 11, p. 1700-1713, NOV 2016. Web of Science Citations: 11.

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