Evaluation of the efficacy of Bj-PRO-10c in the prevention and treatment of cachexia induced by Pancreatic Cancer

• Grant number: 19/08999-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): November 01, 2019
• Effective date (End): March 20, 2021
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Claudiana Lameu
• Grantee: Caio Vinícius Teles Rossini
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/19128-2 - Metastasis mechanisms of childhood tumors to bone marrow, AP.JP

Abstract

Cachexia is a complex metabolic syndrome characterized by loss of muscle mass, anorexia, Anemia, fatigue and altered lipid metabolism which is often associated with severe chronic diseases, including advanced Cancer (especially Pancreatic Cancer). The syndrome is characterized by a negative energy and protein balance, a physiological response triggered by the underlying disease that mobilizes proinflammatory cytokines that mediate organ-organ crosstalk existing in cachexia. However, other mediators have been identified in the pathophysiology of cachexia to induce a systemic effect, including components of the renin-angiotensin system, particularly angiotensin II (Ang II) and reactive oxygen/nitrogen species, as well as Nitric Oxide (NO). Thus, it is interesting to elaborate a robust multimodal approach capable of acting in different signaling pathways involved in the syndrome for the prevention or treatment of the observed changes. Bj-PRO-10c, a proline rich antihypertensive peptide isolated from Bothrops jararaca venom has as its molecular targets, the Angiotensin Converting Enzyme (ACE) and Argininosuccinate Synthase (ASS), therefore the mechanism of action involves inhibition of formation of Ang II and induction of L-arginine/NO recycling. Regarding that, the objective of this project is to obtain original and relevant information on the efficacy of Bj-PRO-10c in the prevention and treatment of Pancreatic Cancer-induced cachexia using a patient-derived xenograft model. Research into the effects induced by Bj-PRO-10c may open up opportunities for the development of drugs that explore new therapeutic strategies blocking the signal transduction pathways of cachexia and increasing patient survival. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GUIMARAES, LARA M. F.; ROSSINI, CAIO V. T.; LAMEU, CLAUDIANA. Implications of SARS-Cov-2 infection on eNOS and iNOS activity: Consequences for the respiratory and vascular systems. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 111, p. 64-71, JUN 1 2021. (19/08999-3, 15/19128-2)

COUTINHO, FERNANDA; GUIMARAES, LARA M. F.; SEEGER, RODRIGO; SANTOS, ANA PAULA J.; GLASER, TALITA; YAMAMOTO, DENISE; LACERDA, LUCAS; ARNAUD-SAMPAIO, VANESSA; ROSSINI, CAIO V. T.; RABELO, IZADORA; et al. Bj-PRO-10c, as an allosteric regulator of argininosuccinate synthase, is a potential therapy for neuroblastoma metastasis. Toxicon, v. 233, p. 9-pg., 2023-09-01. (13/07937-8, 16/11098-0, 18/18799-9, 19/17483-0, 15/19128-2, 22/11093-9, 19/08999-3, 18/07366-4)