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Evaluation of rock kinases and their interaction with microRNAs in bone sarcomas of childhood: implications for tumor progression and invasion

Abstract

The treatment of childhood cancer has evolved significantly in recent decades. However, the cure rates obtained for certain histological subtypes, such as malignant high-grade brain tumors, aggressive subtypes of leukemias and sarcomas are mostly lagging behind. Ewing's sarcoma and osteosarcoma represent the most frequent malignant bone tumors , representing 5-7 % of all cancers affecting children. Both tumor types are initially considered curable, though they present a great propensity for metastasis and relapses due to the inherent chemoresistance and invasiveness of cells. Recently, ROCK kinases have been identified as important contributors in the pathophysiology and progression of different tumors due to their role in cell migration. In fact, different studies suggest that blocking elements involved in the control of cell migration can reduce the opportunistic ability of tumor cells to invade and metastasize to distant organs, a step considered critical in goal-directed intervention. Thus, we propose to evaluate the expression of ROCK1 and ROCK2 genes and associated microRNAs in samples of pediatric patients affected with osteosarcoma and Ewing's sarcoma and to evaluate the in vitro effects of ROCK kinases inhibition in cell lines from these bone tumors, emphasizing on the processes of proliferation, migration and invasion. Moreover, we also aim to assess the influence of ROCK inhibition on resistance and sensitization to treatments currently available for each tumor type. In parallel, in vivo experiments in immunodeficient mice will be conducted in order to study the therapeutic potential of the inhibition of the kinases targeted towards tumor dissemination. (AU)

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Scientific publications (6)
(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)
DE SOUSA, GRAZIELLA RIBEIRO; VIEIRA, GABRIELA MACIEL; DAS CHAGAS, PABLO FERREIRA; PEZUK, JULIA ALEJANDRA; BRASSESCO, MARIA SOL. Should we keep rocking? Portraits from targeting Rho kinases in cancer. PHARMACOLOGICAL RESEARCH, v. 160, OCT 2020. Web of Science Citations: 1.
ROBERTO, GABRIELA MOLINARI; LIRA, REGIA CAROLINE; DELSIN, LARA ELIS; VIEIRA, GABRIELA MACIEL; SILVA, MARCELA OLIVEIRA; HAKIME, RODRIGO GUEDES; YAMASHITA, MAURICIO EIJI; ENGEL, EDGARD EDUARD; SCRIDELI, CARLOS ALBERTO; TONE, LUIZ GONZAGA; BRASSESCO, MARIA SOL. microRNA-138-5p as a Worse Prognosis Biomarker in Pediatric, Adolescent, and Young Adult Osteosarcoma. Pathology & Oncology Research, v. 26, n. 2, p. 877-883, APR 2020. Web of Science Citations: 4.
ROBERTO, G. M.; DELSIN, L. E. A.; VIEIRA, G. M.; SILVA, M. O.; HAKIME, R. G.; GAVA, N. F.; ENGEL, E. E.; SCRIDELI, C. A.; TONE, L. G.; BRASSESCO, MARIA SOL. ROCK1-PredictedmicroRNAs Dysregulation Contributes to Tumor Progression in Ewing Sarcoma. Pathology & Oncology Research, v. 26, n. 1, p. 133-139, JAN 2020. Web of Science Citations: 4.
DELSIN, L. E. A.; ROBERTO, G. M.; FEDATTO, P. F.; ENGEL, E. E.; SCRIDELI, C. A.; TONE, L. G.; BRASSESCO, M. S. Downregulated Adhesion-Associated microRNAs as Prognostic Predictors in Childhood Osteosarcoma. Pathology & Oncology Research, v. 25, n. 1, p. 11-20, JAN 2019. Web of Science Citations: 2.
ROBERTO, GABRIELA MOLINARI; VIEIRA, GABRIELA MACIEL; ALBERICI DELSIN, LARA ELIS; SILVA, MARCELA DE OLIVEIRA; HAKIME, RODRIGO GUEDES; ENGEL, EDGARD EDUARD; SCRIDELI, CARLOS ALBERTO; TONE, LUIZ GONZAGA; BRASSESCO, MARIA SOL. MiR-708-5p is inversely associated with EWS/FLI1 Ewing sarcoma but does not represent a prognostic predictor. CANCER GENETICS, v. 230, p. 21-27, JAN 2019. Web of Science Citations: 2.
VIEIRA, GABRIELA MACIEL; ROBERTO, GABRIELA MOLINARI; LIRA, REGIA CAROLINE; ENGEL, EDGARD EDUARD; TONE, LUIZ GONZAGA; BRASSESCO, MARIA SOL. Prognostic value and functional role of ROCK2 in pediatric Ewing sarcoma. Oncology Letters, v. 15, n. 2, B, p. 2296-2304, FEB 2018. Web of Science Citations: 0.

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