| Grant number: | 13/26344-8 |
| Support Opportunities: | Regular Research Grants |
| Start date: | June 01, 2014 |
| End date: | May 31, 2016 |
| Field of knowledge: | Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology |
| Principal Investigator: | Maria Cláudia Nogueira Zerbini |
| Grantee: | Maria Cláudia Nogueira Zerbini |
| Host Institution: | Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated researchers: | Adhemar Longatto Filho ; Antonio Marcondes Lerario ; Madson Queiroz Almeida ; Maria Candida Barisson Villares Fragoso |
Abstract
Uncontrolled cell proliferation is a key factor in the pathogenesis of neoplasia . In the proliferative process , the neoplastic cells show a preference for anaerobic glycolysis even in the presence of oxygen , a phenomenon known as the " Warburg effect ". The anaerobic metabolism stimulates the conversion of pyruvate to lactic acid, which leads to a reduction of intra cytoplasmic pH. To prevent apoptosis induced by lactic acid , the neoplastic cells develop defense mechanisms, among which the increased transport of lactic acid out of the cell. This explains why many neoplasms end up having significant increases in the expression of monocarboxylate transporters (MCTs). MCTs are among the main regulators involved in pH homeostasis of neoplastic cells . Interestingly , there is a gradual increase in the expression of MCTs during progress from intraepithelial to invasive neoplasia . MCTs family has 14 members; isoforms 1, 2 , 3 and 4 are responsible for extracellular transport of lactic acid across the cytoplasmic membrane. It was recently demonstrated the need for two chaperones (CD44 and CD147) for MCT1 and MCT4 isoforms exert their transport function effectively. in recent years, several studies have demonstrated overexpression of these chaperones on several human malignancies , improving neoplastic cells ability for growth , migration , invasion and angiogenesis. Immunoexpression of glycoprotein CD147 has recognized biological relevance as a prognostic factor in several neoplasms , probably associated with chemotherapy resistance. Studies using immunostaining of CD147 in urothelial carcinoma, carcinomas of the uterine cervix, mesotheliomas and gastrointestinal stromal tumors ( GISTs ), were associated with significant prognostic impact. Neoplasms of the adrenal cortex have been a tremendous challenge regarding the unpredictable biological behavior, particularly in the pediatric age group , making it imperative to find alternative information that can determine with greater accuracy the prognostic of patients with this disease , and consequently establish a correct therapeutic strategy. Studies of the influence of the complex metabolism of fatty tumors of the adrenal cortex has yet to study , to our knowledge . Given the importance of these neoplasms particularly in our geographic area, the absence of literature data related to this molecules in ACTs and the potential use of molecular moderators of glycolytic pathways as prognostic tools and therapeutic targets, we proposed to investigate the role of MCTs and associated molecules in clinically benign and clinically malignant tumors of the adrenal cortex in children and adults. (AU)
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