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POLO-LIKE KINASE IN MEDULLOBLASTOMA: PLKs genes expression evaluation and in vitro effects of pharmacological inhibition of PLK1.

Grant number: 11/01026-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2011
Effective date (End): May 31, 2014
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Luiz Gonzaga Tone
Grantee:Julia Alejandra Pezuk
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Medulloblastoma(MB) is the most common solid tumor in children and, according to the World Health Organization (WHO), is classified as a central nervous system tumor grade IV. Currently, treatment of this type of cancer consists of surgery, chemotherapy and, depending on the patient's age, radiotherapy. Although survival is high (over 50%) treatment used may cause medium and long term adverse effects. Therefore, studies to identify new therapeutic targets are essential to improve treatment for younger patients (of less than three years old) and to reduce the adverse effects caused by the treatment of this disease. The Polo-like kinases(PLKs) comprise a family of five members of serine / threonine kinases: PLK1, PLK2, PLK3, PLK4 and PLK5, which play key roles in cell cycle control. Several studies have shown that the PLK1 gene is down regulated in different tumors types and is also correlated with prognosis and malignancy of some cancers. There are no reports in the literature on changes in the expression of PLK2, PLK4 and PLK5, however PLK3 has been reported down regulated in some cancer types. In this study we will analyze PLK family genes expression in MB cell lines and samples, and concurrently we will evaluate the effects of PLK1 inhibition with BI 2536, BI 6727, GSK461364 and GW843682X in MB cell lines. It will also be assessed and correlated with expression of miRNAs 100, 126 and 593 * 219-5p, related to the family genes PLK.

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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)
RAMOS, PRISCILA M. M.; PEZUK, JULIA A.; CASTRO-GAMERO, ANGEL M.; OLIVEIRA, HARLEY F.; SCRIDELI, CARLOS A.; UMEZAWA, KAZUO; TONE, LUIZ G.. Antineoplastic Effects of NF-kappa B Inhibition by DHMEQ (Dehydroxymethylepoxyquinomicin) Alone and in Co-treatment with Radio-and Chemotherapy in Medulloblastoma Cell Lines. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 18, n. 4, p. 541-549, . (10/18792-2, 11/01026-8)
PEZUK, JULIA ALEJANDRA; BRASSESCO, MARIA SOL; MANZINI RAMOS, PRISCILA MARIA; SCRIDELI, CARLOS ALBERTO; TONE, LUIZ GONZAGA. Polo-Like Kinase 1 Pharmacological Inhibition as Monotherapy or in Combination: Comparative Effects of Polo-Like Kinase 1 Inhibition in Medulloblastoma Cells. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 17, n. 9, p. 1278-1291, . (11/11287-3, 11/01026-8)
PEZUK, JULIA ALEJANDRA; BRASSESCO, MARIA SOL; DE OLIVEIRA, RICARDO SANTOS; MACHADO, HELIO RUBENS; NEDER, LUCIANO; SCRIDELI, CARLOS ALBERTO; TONE, LUIZ GONZAGA. PLK1-associated microRNAs are correlated with pediatric medulloblastoma prognosis. CHILD'S NERVOUS SYSTEM, v. 33, n. 4, p. 609-615, . (11/11287-3, 11/01026-8)

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