Hypothalamic changes related to the syndrome of cachexia associated with cancer: morphological analysis and histological, molecular, cellular and systemic central nervous system study

• Grant number: 16/12508-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2016
• End date: April 30, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marilia Cerqueira Leite Seelaender
• Grantee: Estefania Simoes Fernandez
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 18/24557-8 - The role of the mTOR pathway in cancer cachexia: a post-mortem neuropathological study, BE.EP.DD

Abstract

Cancer caquexia is defined as a multifactorial syndrome characterized by continued loss of skeletal muscle mass (with or without loss of fat mass), associated with the presence of systemic inflammation, with the following symptoms: asthenia, anorexia, anemia, and fatigue. It is believed that metabolic changes are triggered by tumor factors, factors secreted by the host and also their interaction. In this context, the Central Nervous System (CNS) is a central point that can be affected by cachexia. However, knowledge about the involvement of the syndrome in the etiology of the CNS is quite scarce. Thus, this project aims to determine possible changes in brain structures of subjects with cachexia associated with cancer and also examines the correlation of these changes with the inflammatory status of the patients. For the study will be recruited, on the university hospital of USP, 30 patients with gastrointestinal cancer, aged 40 to 80 years, of both sexes, who after agreeing to participate and sign the informed consent form, will be divided into two groups: Without Cancer Cachexia (WSC) and with Cancer Cachexia (CC). The experimental protocol will consist of body composition assessment, psychometric and cognitive tests, blood collection for serum inflammatory parameters, gastrointestinal tissue collection for molecular analysis of factors related to inflammation and neuropeptides linked to eating behavior and finally, examination of brain magnetic resonance imaging (VBM, IDT, fMRI and RMEs). These results will be analyzed and correlated with the aid of Statistics Sector of the USP Institute of Biomedical Sciences and invested in scientific publications. (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)

DE CASTRO, GABRIELA S.; CORREIA-LIMA, JOANNA; SIMOES, ESTEFANIA; ORSSO, CAMILA E.; XIAO, JINGJIE; GAMA, LEONARDO R.; GOMES, SILVIO P.; GONCALVES, DANIELA CAETANO; COSTA, RAQUEL G. F.; RADLOFF, KATRIN; et al. Myokines in treatment-naive patients with cancer-associated cachexia. Clinical Nutrition, v. 40, n. 4, p. 2443-2455, APR 2021. (16/12508-7, 12/50079-0, 16/13810-9, 13/25207-7, 16/02780-1)

DE CASTRO, GABRIELA S.; SIMOES, ESTEFANIA; LIMA, JOANNA D. C. C.; ORTIZ-SILVA, MILENE; FESTUCCIA, WILLIAM T.; TOKESHI, FLIVIO; ALCANTARA, PAULO S.; OTOCH, JOSE P.; COLETTI, DARIO; SEELAENDER, MARILIA. Human Cachexia Induces Changes in Mitochondria, Autophagy and Apoptosis in the Skeletal Muscle. CANCERS, v. 11, n. 9, SEP 2019. (16/02780-1, 12/50079-0, 16/13810-9, 16/12508-7, 17/12260-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FERNANDEZ, Estefania Simoes. Central nervous system alterations associated with cancer cachexia: in vivo neuroimaging and post-mortem neuropathological analysis.. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.