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Definition of new therapeutic strategies based on the “re-education" of the microenviroment
Universita degli Studi di Udine
Istituto di Anatomia Patologica, Azienda Ospedaliero Universitaria di Udine, Ple S. Maria della Misericordia 15, 33100 Udine (Italy)
Prof. Carla Di Loreto
Dr. Daniela Cesselli Dr. Antonio Paolo Beltrami
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
Translational medicine aims to transfer the advances in basic scientific research to define innovative approaches for the diagnosis and treatment of diseases. With this specific purpose, our research group is focused on the use of human adult stem cells isolated from human gliomas as an approach to personalize medicine and identify new prognostic and predictive factors of response to therapy and design new therapeutic strategies. In particular, the collaboration with neurosurgery led to the demonstration that in gliomas, in addition to stem cells capable of starting the tumor (GSC), there is a population of stem cells, devoid of genetic mutations that characterize the tumor, but able to support the growth of the tumor itself. These cells, called GASC (glioma-associated stem cells) are able, through the release of extracellular vesicles (e.g. exosomes), to increase the biological aggressiveness of the glioma-initiating cells.
What is the aim of the project?
The aim of the project is to develop new therapeutic strategies with the purpose of targeting the tumor microenvironment of human gliomas.
What techniques and methods are used?
We will use glioma associated stem cells (GASC), our patient-based in vitro model of the tumor microenvironment, to evaluate pathways possibly responsible for activation, immunomodulatory properties and tumor supporting function of the glioma microenvironment (NGS of mRNA and miRNA have been already berformed). To demonstrate whether it is possible to act on the stroma to reduce the immunomodulatory- and tumor supporting- function of the tumor microenvironment, we will treat GASC with drugs and/or miRNA/antagomir and will verify if GASC lose their ability to support the cancer cells. The most promising therapeutic strategies will be tested in an animal model of orthotopic xenograft glioma, recently optimized in our group.
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
- The student will be included in a team already working in this project and will follow - for the time he/she will be in the lab - all the activities - including cell culture - microscopy - flow-cytometry - data collection - discussion of results with statistician - neurosurgeon and pathologist. Culture of stem cells from human gliomas In vitro assays to evaluate drug sensitivity Characterization of cells by immunofluorescence and confocal microscopy. Flow-cytometry
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
At the beginning of the collaboration, the student will recieve papers and all the theroretical and practical information required for work in the project.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Student must be: 1. strongly committed to be involved in a research program including several basic-research activities and 2. able to work in a team.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- Bourkoula E; et al. Glioma-associated stem cells: a novel class of tumor-supporting cells able to predict prognosis of human low-grade gliomas. Stem Cells. 2014;32(5):1239-1253.
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