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Evaluation of the antitumor effects of the inhibition in vitro of the AP-1 transcription factor by DTCM-g in adult and pediatric glioblastoma

Grant number: 13/23239-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2014
Effective date (End): December 31, 2014
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:María Sol Brassesco Annichini
Grantee:Gabriela Molinari Roberto
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Glioblastoma represents 50% of the brain tumor in adults; being less frequent in children (9%). Despite the therapeutic advances, the median survival of glioblastoma patients is still dismal, around one year. Treatment of this tumor is generally hampered by its invasive nature that leads to a high rate of recurrence after surgery, and its resistance to apoptosis and to conventional drugs. The transcription factor AP-1 is an important point of convergence of many pathways including proliferation, apoptosis and invasion. In glioblastomas, the c-Jun subunit of AP-1 is found hyperphosphorylated and therefore more active to act on gene transcription. In this situation, c-Jun develops an important role increasing the expression of several genes involved on cell proliferation, apoptosis and tumor invasion. Recently, a new specific AP-1 inhibitor called DTCM-g was synthesized. This inhibitor blocks the phosphorylation of c-Jun, preventing its translocation into the nucleus. DTCM-g has already shown antitumor activity in osteosarcoma and bladder cancer, however its potential antiproliferative effects in glioblastoma are still unknown. In view of this, this project aims to study the influence of AP-1 inhibition by DTCM-g on tumor growth and invasion in adult and pediatric glioblastoma cell lines, based on functional tests and on the expression dinamics of genes under its regulation.

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)
ROBERTO, GABRIELA MOLINARI; PAIVA, HELDER HENRIQUE; BOTELHO DE SOUZA, LUCAS EDUARDO; PEZUK, JULIA ALEJANDRA; VIEIRA, GABRIELA MACIEL; DE OLIVEIRA, HARLEY FRANCISCO; UMEZAWA, KAZUO; TONE, LUIZ GONZAGA; BRASSESCO, MARIA SOL. DTCM-glutarimide Delays Growth and Radiosensitizes Glioblastoma. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 18, n. 9, p. 1323-1329, 2018. Web of Science Citations: 0.

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