TRIGBM

Identification of TRAIL sensitivity/resistance mechanisms and searching for novel TRAIL-sensitizing agents in Glioblastoma Multiforme

Coordinatore	KOC UNIVERSITY    more  Organization address address: RUMELI FENERI YOLU SARIYER city: ISTANBUL postcode: 34450 contact info Titolo: Mrs. Nome: Askim Cognome: Demiryurek Email: send email Telefono: +90 212 3381333 Fax: +90 212 3381205
Nazionalità Coordinatore	Turkey [TR]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-CIG
Funding Scheme	MC-CIG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-09-01   -   2017-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	KOC UNIVERSITY  Organization address address: RUMELI FENERI YOLU SARIYER city: ISTANBUL postcode: 34450 contact info Titolo: Mrs. Nome: Askim Cognome: Demiryurek Email: send email Telefono: +90 212 3381333 Fax: +90 212 3381205	TR (ISTANBUL)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'The overall goal of this proposal is to explore the molecular basis of TRAIL-response in an aggressive brain cancer, Glioblastoma Multiforme (GBM), and identify new reagents that will augment the TRAIL response of GBMs. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL), emerged as a prime candidate for cancer treatment due to its tumor-specificity, however its clinical success is likely limited by the innate or acquired resistance of some tumors to TRAIL. Dr. Bagci-Onder will address whether aberrant expression or activity of apoptotic program components is associated with TRAIL-resistance in GBMs. Specifically, she will address the role of a pro-apoptotic factor, harakiri (HRK), that she found to be significantly repressed in the TRAIL-resistant subpopulation of a primary GBM cell line. The potential role of this hitherto unstudied protein in GBM cell TRAIL response will be uncovered using expression analysis and functional assays in a large panel of GBM lines with varying TRAIL responses. Since multiple components of TRAIL signaling might be misregulated in TRAIL-resistant cells, Dr. Bagci-Onder will generate dual bioluminescent reporter systems of HRK and other TRAIL-associated factors, such as TRAIL receptors DR4/DR5; TRAIL signaling inhibitor proteins Flip, XIAP and Bcl-2 to assess gene expression changes. It is becoming evident that TRAIL-based combinatorial therapies with additional agents that can augment the TRAIL-response of tumors are more efficacious than using TRAIL alone. Using the novel reporter systems, Dr. Bagci-Onder will screen for novel TRAIL-sensitizing agents to identify potential TRAIL-sensitizers among FDA-approved chemicals. The function of these agents will be validated in mouse xenograft GBM models using neural stem cells as vehicles for TRAIL delivery. Together, this project will further the understanding of GBM biology and lead to potential clinical applications.'