Evaluation of the effectiveness of Bj-PRO-10c in the prevention and treatment of pancreatic cancer-induced cachexia

Author(s)

Caio Vinicius Teles Rossini

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2023-08-14

Examining board members

Claudiana Lameu

• Advisor: Claudiana Lameu

Abstract

Pancreatic ductal adenocarcinoma (PDA) is a lethal neoplasm often associated with cachexia, a syndrome characterized by excessive weight loss, muscle wasting, reduced adipose tissue and physical impairment, resulting in malnutrition, anorexia and decreased quality of life and survival. Cancer cachexia is divided into three clinically relevant stages: pre-cachexia (\"mild\"), cachexia, and refractory cachexia (\"severe\"); where progression depends on factors such as systemic inflammation, tumor type and stage, food intake, and response to treatment. Currently, there are no prevention methods available for cachexia and treatment in cachectic patients is palliative and multimodal, that is, there is no established standard therapy. In view of this scenario, the present study sought to establish two models of cachexia using fragments of PDA tumors from two patients (P08 and P12) and to evaluate the effect of chronic administration of the peptide Bj-PRO-10c, which acts on two signaling pathways related to cachexia. Interestingly, the PDA transplant from patient 12 caused \"mild\" cachexia, while that from patient 08 resulted in a more severe form of the syndrome, in line with the clinical findings of the donors. Bj-PRO-10c exhibited protective effects against weight loss, muscle atrophy, adipose tissue reduction, and oxidative stress associated with PDA-induced cachexia. The peptide reduced superoxide anion production in pancreatic tumor cells, preserved body weight in advanced stages of the disease, and attenuated muscle and adipose degradation, without affecting tumor growth. These results highlight the importance of further research to develop effective therapies that target cachexia signaling pathways, improving survival and quality of life for patients with PDA. (AU)

• FAPESP's process: 19/08999-3 - Evaluation of the efficacy of Bj-PRO-10c in the prevention and treatment of cachexia induced by Pancreatic Cancer
• Grantee: Caio Vinícius Teles Rossini
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)