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Pathological asocciation between obesity and development, progression and agresiveness of diferent endocrine-related cancers
Spain (IFMSA-SPAIN)-University of Cordoba, Cordoba
Edificio IMIBIC; Hospital Univ. Reina Sofia, Av. Menendez Pidal s/n; 14004, Córdoba
Raul M. Luque
Raul M. Luque
Type of Research Project
- Basic science
What is the background of the project?
Obesity (OB) is a chronic endocrine-metabolic disease and an emerging global epidemic that represents a capital health problem, since it increases the risk of developing severe endocrine (diabetes) and cardiovascular pathologies, as well as certain types of cancer, especially those named endocrine- reated cancer (e.g. Prostate and breast cancers, neuroendocrine tumors, etc.). These endocrine- related cancers are a heterogeneous and complex tumor types, whose marked, patient-dependent phenotypic/clinical variability (e.g. aberrant expression of molecules) is profoundly influenced by OB, which is indeed associated with increased incidence, aggressiveness and resistance to drugs. All these features hinder the identification of key, common elements, which could help to develop more effective diagnostic and therapeutic strategies. Thus, despite the magnitude of this health problem and its associated healthcare costs, the molecular, cellular and endocrine-metabolic mechanisms underlying the IFMSA International Secretariat, c/o IMCC, Nørre Allé 14, 2200 København N., Denmark pathological association between OB and many endocrine-related cancers are still unknown.
What is the aim of the project?
In this project, we will deploy a set of innovative clinical and experimental approaches commonly used in our team, including numerous clinical samples and cellular and animal models, in order to identify new diagnostic, prognostic and therapeutic opportunities in the interaction between metabolic dysregulations (mainly obesity) and tumoral pathologies (endocrine-related cancers), in order to promote their transfer to the Society and improve the Public Health Systems We specifically will be focus on the study of cellular, molecular and pathophysiological bases that underlie the development and progression of metabolic diseases (such as obesity and diabetes), tumor pathologies and cancer and, on the pathophysiological association and interaction between both pathologies. More specifically, we have special interest in the study of the function of some endocrine-metabolic factors (hormonal, inflammatory and lipidic systems, chemokines, miRNAs, etc.), as well as the molecular and cellular mechanisms underlying in the pathophysiological relationship between obesity and cancer, including: 1) the machineries that control the expression and secretion of inflammatory components (inflammasome); 2) regulators of the senescence-associated secretory phenotype (SASP); 3) factors associated with the regulation of the expression and secretion of miRNAs (DROSHA, DICER, etc.) and extracellular vesicles; and, 4) machineries and factors that control the splicing process [spliceosome and non-sense mediated mRNA decay (NSMD) and related factors/variants], etc.
What techniques and methods are used?
In this project we will use: 1) Immunohistochemestry microscopy-based technique. 2) Western blot (inmmunoblot) techniques. 3) Real time-PCR (polymerase chain reaction). 4) Cell migration and invasion assays. 5) Cytotoxicity assays.
What is the role of the student?
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The tasks that the student should be accomplished by his/her self include: To get familiar with all the procedures involved in metabolic dysregulations and tumoral pathologies. To learn different cellular and molecular techniques (cell cultures, real time RT-PCR, immunohistochemestry, western-blot) and to be involved in the development and discussion of results of the research. She / he will investigate an interesting issue within the above described project. The student will have opportunity to help analyzing the data.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Preliminary readings from already published works from the group to understand better the project and specific reading and training in the technics that he/she will be used with the pocodyte cultures.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Any laboratory experience will be well appreciated. Subjects passed: Biochemistry and molecular biology, physiology. Capacity of interaction and communication skills. Active and positive attitude
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system - Students in biomedical fields
- Changes in Splicing Machinery Components Influence; Precede; and Early Predict the Development of Type 2 Diabetes: From the CORDIOPREV Study. Gahete MD; Del Rio-Moreno M; Camargo A; Alcala- Diaz JF; Alors-Perez E; Delgado-Lista J; Reyes O; Ventura S; Perez-Martínez P; Castaño JP; Lopez- Miranda J; Luque RM. EBioMedicine. 2018 Nov;37:356-365. doi: 10.1016/j.ebiom.2018.10.056. Epub 2018 Nov 13.
- Biguanides exert antitumoral actions in pituitary tumor cells through AMPK-dependent and -independent mechanisms. Vázquez-Borrego MC; Fuentes-Fayos AC; Herrera Martínez AD; L-López F; Ibáñez-Costa A; Moreno Moreno P; Alhambra-Expósito MR; Barrera-Martín A; Blanco-Acevedo C; Dios E; Venegas-Moreno E; Solivera J; Gahete MD; Soto-Moreno A; Gálvez- Moreno MA; Castaño JP; Luque RM. J Clin Endocrinol Metab. 2019 Mar 12. pii: jc.2019- 00056. doi: 10.1210/jc.2019-00056. [Epub ahead of print]
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