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Effect of histone deacetylase and proteasome inhibitors in Glioma models

Grant number: 20/08987-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2021
Effective date (End): December 31, 2023
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal researcher:Leticia Veras Costa Lotufo
Grantee:Luciana Costa Furtado
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds, AP.BTA.TEM


Gliomas are tumors of the Central Nervous System that affect mainly the adult population, imposing a low survival rate, and the most frequent type, glioblastoma, is characterized by high aggressiveness and a poor prognosis. The search for new therapies is essential in order to bring not only more drug options, but also the possibility of innovative treatments, including new therapeutic targets and combined therapies with greater effectiveness and fewer side effects. In this context, proteasome inhibitors (PI) and histone deacetylase inhibitors (IHDAC) have been studied in vitro and in vivo glioma models with promising results. Thus, in the present work, we propose to investigate the promoted effects by proteasome inhibitors (bortezomib, carfilzomib, dihydroeponemycin and marizomib) and histone deacetylase inhibitors (vorinostat and unpublished substances related to PCI-34051) in glioma models submitted to individual treatment or with the combination of substances. To evaluate the effects, two-dimensional and three-dimensional cell culture models will be used, in addition to the co-culture of astrocytes and glioma cells. The studies of the mechanisms of action are based on a combined approach of phenotypic and molecular assays evaluating gene expression (real-time PCR and transcriptomics) and protein modulation (western blotting and proteomics) both of the pathways directly related to the targets of the substances (proteasome and HDAC), as well as cell death pathways.

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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)
NISHIMURA, V, RODOLFO H.; DOS SANTOS, THIAGO; MURIE, VALTER E.; FURTADO, LUCIANA C.; COSTA-LOTUFO, V, LETICIA; CLOSOSKI, GIULIANO C. Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents. Beilstein Journal of Organic Chemistry, v. 17, p. 2968-2975, DEC 22 2021. Web of Science Citations: 0.

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