Research Grants 24/01682-2 - Capacidade funcional, MicroRNAs - BV FAPESP
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Characterization of circulating extracellular vesicles in patients with colorectal cancer.

Abstract

Patients with colorectal cancer (CRC) exhibit changes in muscle tissue characterized by a reduction in muscle quantity, quality, and function. These conditions lead to sarcopenia and myosteatosis. Consequently, patients experience a decrease in functional capacity and early development of frailty. Recently, literature data have shown that extracellular vesicles (EVs) play an important role in inter-tissue signaling. Experimental studies have shown that circulating EVs can alter muscle phenotype and metabolism. It is worth noting that EVs can transport microRNAs; however, the role of microRNAs carried by circulating EVs in muscle phenotype and function in CRC patients has not yet been elucidated. Therefore, our group is interested in understanding the characteristics (number, size, microRNA load, and percentage of tumor origin) of circulating EVs in CRC patients with different levels of functional capacity. Additionally, we aim to understand whether muscle phenotype, as well as the degree of adiposity and tumor stage, may also contribute to altering these characteristics. Our hypothesis is that patients with reduced functional capacity will present a different number, size, and load of circulating EVs compared to patients without reduced functional capacity. Furthermore, we hypothesize that patients with low functional capacity have a higher percentage of circulating EVs of tumor origin. To this end, 80 patients diagnosed with CRC will be invited to participate in the study. The participants will undergo: 1) analysis of clinical and physical data; 2) computed tomography (CT); 3) functional capacity assessment through the 6-minute walk test, 5-time sit-to-stand test, and frailty phenotype; and 4) blood collection. Subsequently, the following will be performed: 1) characterization of tumor stage according to clinical data; 2) characterization of functional capacity according to functional tests; 3) assessment of muscle quantity and quality, as well as visceral and subcutaneous adiposity, through CT; 4) isolation and characterization of circulating extracellular vesicles in collected blood; and 5) evaluation of the expression of microRNAs carried by circulating EVs. Finally, the EV characteristics will be compared according to functional capacity, muscle phenotype, degree of visceral and subcutaneous adiposity, and tumor stage. (AU)

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