FINDING AND VALIDATING MOLECULAR TARGETS IN GASTRIC TUMOR STEM CELLS FOR DEVELOPMENT OF NOVEL ANTI-CANCER THERAPEUTIC STRATEGIES.
Program: Resurse Umane
Project code: TE-100/2010
Project’s length: 36 months (August 2010 – July 2013)
Host institution: Stefan S. Nicolau Institute of Virology (www.virology.ro)
Address: Mihai Bravu 285 Ave., sector 3, Bucharest, Romania; tel/fax: 021 3242590
Project director: Dr. Mihaela CHIVU ECONOMESCU, CSIII
e-mail: firstname.lastname@example.org; email@example.com
Budget: 750.000 lei
Summary of the project
Cellular heterogeneity, present in most solid tumors, represents an enormous challenge for cancer eradication. Present strategies for inducing cell death usually target only the most rapidly proliferating cells within a tumor, and are unable to destroy tumor stem cells that are more resistant to standard chemotherapeutic agents and have the ability to regenerate the tumor. It became increasingly obvious that it is necessary to develop strategies targeted to the mechanisms of survival and regeneration characteristics of tumor stem cells.
A recent study published in 2009, which identify gastric tumor stem cells (gtsc) based on surface antigen cd44, opens new directions for the
management of gastric carcinoma, disease that is the second cause of death worldwide (700,000 deaths/year worldwide ; 17/6.6 m / f deaths/100000 people/year in Romania).
Given the opportunity to identify and isolate gtsc, and our laboratory experience in the field of stem cells and anti-tumor therapy, we intend to use small interferece rna technology to specifically inhibit certain genes overexpresed in gastric cancer which can be promoters of processes such as: cell proliferation, interaction with the matrix, motility, metastasis, angiogenesis.
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1. Identification, isolation and characterization gtsc. Testing their tumoral capacity on immunodeficient animal models
2. Identification of molecular targets by testing gene expression in the gtsc, and selection of genes significantly modified
3. Specific inhibition of selected gene expression using sirna methodology
4. Analysis of molecular target therapy-induced effects on gtsc functionality.
Phase I (15 August 2010 – 10 December 2010)
Objective: Identification, isolation and characterization of stem cells in gastric tumor cell lines and primary cultures of gastric adenocarcinoma.
Budget: 110.000 lei
Selection protocol for gastric tumor stem cells isolation.
Considerations on the performances of the proposed selection method.
An original article accepted for publication in Hepato-Gastroenterology.
Phase II (16 December 2010 – 30 November 2011)
Objective 1: Testing tumorigenic capacity of isolated gastric tumor stem cells in immunodeficient animal models.
Objective 2: Identification of molecular targets by testing gene expression in gastric tumor stem cells, and selection of genes significantly
Budget: 225.000 lei
Phase III (1 December 2011 – 30 November 2012)
Objective 1: Specific inhibation of target gene expression using siRNA technology.
Objective 2: In vitro analysis of molecular target therapy effects on the functionality of gastric tumor stem cells.
Budget: 252.000 lei
Phase IV (1 December 2012 – 15 July2013)
Objective 1: In vivo analysis of molecular target therapy effects on the functionality of gastric tumor stem cells.
Objective 2: Final analysis of results and conclusions.
Budget: 148.000 lei
The research team
Mihaela CHIVU ECONOMESCU, PhD
Drd. Laura G. NECULA, PhD St
Drd. Denisa Laura DRAGU, PhD St
Cosmin Ilie STANCU, MD