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Impact of Aerobic Exercise Training on cancer-induced cachexia in mice lacking Heme oxygenase-1 expression in skeletal muscle.

Grant number: 23/13382-0
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): February 20, 2024
Effective date (End): February 19, 2025
Field of knowledge:Health Sciences - Physical Education
Principal Investigator:Patricia Chakur Brum
Grantee:Ailma Oliveira da Paixão
Supervisor: Leo Edmond Otterbein
Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Harvard University, Boston, United States  
Associated to the scholarship:21/08109-8 - INFLUENCE OF AEROBIC PHYSICAL TRAINING ON HEMOXYGENASE-1 IN THE CONTROL OF MUSCLE MASS AND TUMOR GROWTH IN AN EXPERIMENTAL MODEL OF CANCER-INDUCED CACHEXIA., BP.DR

Abstract

It is already known that aerobic exercise training (AET) attenuates the process of skeletal muscle loss in experimental models of cancer cachexia, becoming an adjuvant therapy for the prevention of muscle mass loss and dysfunction. In addition, AET reduces the incidence of many cancer types, while slowing tumor growth in different cancer models. However, the molecular mechanisms involved in these responses are poorly understood. In this regard, the cytoprotective gene heme oxygenase-1 (HO-1) has been widely studied for its ability to maintain cell homeostasis by sharing anti-inflammatory and antioxidant effects. HO-1 is positively modulated by AET and it has already been described that its upregulation in skeletal muscle attenuates the loss of muscle mass. However, in tumors, the increased HO-1 expression has been associated to tumor cell proliferation, progression, metastasis, and tumor aggressiveness. In my project that has been developed in Brazil, we observed that AET precondition induced an increase in HO-1 gene expression in skeletal muscle of tumor-bearing mice that developed cachexia. Thus, in the present scientific proposal, we aim to evaluate the role of HO-1 in skeletal muscle and in the tumor of HO-1 knockout mice (skeletal muscle specific) submitted to AET for 30 days before tumor cells inoculation.

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