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Biological Role of translational controlled tumor protein in tumor development and reversion (basic and translational oncology)
Brazil (IFMSA-Brazil) - Universidade Federal do Parana (UFPR), Curitiba
Department of Cell Biology, Federal University of Parana, Rua XV de Novembro, 1299 - Centro, Curitiba - PR, 80060-000.
Dr. Rubens Bertazolli Filho
Dr. Andrea Senff-Ribeiro
English and French
Type of Research Project
- Clinical Project without Laboratory work
What is the background of the project?
Tumor reversion is an extremely promising field in translational oncology. The therapeutic goal in tumor reversion is to trigger the tumor cell reprogramming into a less malignant phenotype, instead of inducing cell death (as the majority of chemotherapeutics). In 2016, an opinion article in Nature Cancer Reviews argued for scientists to focus on tumor cell reversion. Authors stated that treatments based on selection and analysis of stable revertants could create more durable remissions by reducing the selective pressure that leads to rapid drug resistance. A key protein in tumor reversion field is TCTP (Translationally Controlled Tumor Protein), which is overexpressed in tumors and is a direct target of sertraline, an antidepressant drug which selectively inhibits serotonin reuptake (SSRI). Thus, it is worth considering the use of SSRIs as a therapeutic possibility, in combination with current treatments.
What is the aim of the project?
The main purpose of this activity to evaluate TCTP levels and expression in tumors and its biological role in the tumor phenotypes and resistance. Study the use of drugs which decrease TCTP levels (as sertraline) for putative therapeutic use in cancer.
What techniques and methods are used?
To achieve the aim of the project, there are analyzed the Human and murine cell culture: to observe the viability, proliferation, migration and clonogenic assays. The analysis aims to evaluate cell parameters and different labeling. Will be a collection of cells from a in vivo model (rats), following to that will be performed a protein electrophoresis (SDS-PAGE) and Immunodetection of proteins: western blotting assays. The technique includes the following process: 1. Wash cells in the tissue culture flask or dish by adding cold phosphate buffered saline (PBS) and rocking gently. Discard PBS. (Tip: Keep tissue culture dish on ice throughout). 2. Add PBS and use a cell scraper to dislodge the cells. Pipette the mixture into microcentrifuge tubes. 3. Centrifuge at 1500 RPM for 5 minutes and discard the supernatant. 4. Add 180 μL of ice cold cell lysis buffer with 20 μL fresh protease inhibitor cocktail. (Tip: If protein concentration is not high enough at the end, it is advised to repeat the procedure with a higher proportion of protease inhibitor cocktail). 5. Incubate for 30 minutes on ice, and then clarify the lysate by spinning for 10 minutes at 12,000 RPM, at 4°C. 6. Transfer supernatant (or protein mix) to a fresh tube and store on ice or frozen at -20°C or -80°C. 7. Measure the concentration of protein using a spectrophotometer. After, the results will be organized in Microsoft Excell and analyzed by the study group.
What is the role of the student?
- 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?
It will be expected from the incomings student: To participate in study groups, to join fieldwork by collecting data from patients in “Unidades Básicas de Saude” (Basic Health Units).To present and attend to seminars in the themes of Public Health, “Saude da Família” Program (Family Health Programa), Epidemiology. To attend to classes of Public Health, Health Practices and Epidemiology at UEPG that will be ministrated in English when exchange students will be present. To apply questionnaires (e.g. CEATHIV - of the Assessment of Adherence to Antiretroviral Therapy Questionnaire, Brazilian adaptation) to the patients during consults. The student will be supervised by the doctor during the appliance. To analyze, process and interpret data.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
There are seminars of the group every week when results and literature are discussed.
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 - The student will prepare a presentation - The student will prepare a scientific report - The student will prepare an abstract
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Be able to work in group and with older people. Subjects passed: Molecular and Cell Biology, Biochemistry and Genetics.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Pre-Medical students from the American-British system - Students in biomedical fields
- 1. Boia-Ferreira et al.; 2017 TCTP as a therapeutic target in melanoma treatment. British Journal of Cancer 2017;117(5):656-665. doi: 10.1038/bjc.2017.230.
- 2. Powers S; Pollack RE. 2016. Inducing stable reversion to achieve cancer control. Nat Rev Cancer. 2016 Apr;16(4):266-70. doi: 10.1038/nrc.2016.12.
- 3. Amson et al.; 2013. Lessons from tumor reversion for cancer treatment. Curr Opin Oncol. 2013 Jan;25(1):59-65. doi: 10.1097/CCO.0b013e32835b7d21. Review.
- Telerman A; Amson R. 2009 The molecular programme of tumour reversion: the steps beyond malignant transformation. Nat Rev Cancer. 2009 Mar;9(3):206-16. Review. doi: 10.1038/nrc2589.
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