Cancer cachexia is a complex disorder characterized by inflammatory responses, and it is associated with poor performance status and high mortality rate of cancer patients. Carboxyamidotriazole (CAI), a noncytotoxic chemotherapy agent, shows anti-inflammatory features in the treatment of many diseases. Here, we investigated the preventive and therapeutic effects of CAI on muscle loss that occurred in mice with advanced Lewis lung carcinoma (LLC). The carcass weights of CAI-treated mice were significantly higher than that of mice in the vehicle group from Day 19 to the end of the study. The gastrocnemius and epididymal adipose tissue weights were also increased by CAI treatment. The protective mechanisms might be attributed to the following points: CAI treatment inhibited the proteolysis in muscles by decreasing expressions of muscle-specific FoxO3 transcription factor and ubiquitin E3 ligases (MuRF1 and atrogin1). Moreover, CAI restricted the NF-κB signaling, downregulated the level of TNF-α in muscle and both TNF-α and IL-6 levels in serum, directly stimulated SIRT1 activity in vitro, and increased SIRT1 content in muscle. These results indicate that CAI can alleviate muscle wasting and is a promising drug against lung cancer cachexia.
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http://dx.doi.org/10.1007/s00210-017-1345-8 | DOI Listing |
Funct Integr Genomics
January 2025
Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, USA.
Large-scale, pan-cancer analysis is enabled by data driven knowledge bases that link tumor molecular profiles with phenotypes. A debilitating cancer-related phenotype is skeletal muscle loss, or cachexia, which occurs partly from tumor products secreted into circulation. Using the LinkedOmicsKB knowledge base assembled from the Clinical Proteomics Tumor Analysis Consortium proteogenomic analysis, along with catalogs of human secretome proteins, ligand-receptor pairs and molecular signatures, we sought to identify candidate pan-cancer proteins secreted to blood that could regulate skeletal muscle phenotypes in multiple solid cancers.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2025
Department of Physical Therapy, University of Florida Health Cancer Center, Gainesville, Florida, USA.
Background: Cancer cachexia represents a debilitating muscle wasting condition that is highly prevalent in gastrointestinal cancers, including pancreatic ductal adenocarcinoma (PDAC). Cachexia is estimated to contribute to ~30% of cancer-related deaths, with deterioration of respiratory muscles suspected to be a key contributor to cachexia-associated morbidity and mortality. In recent studies, we identified fibrotic remodelling of respiratory accessory muscles as a key feature of human PDAC cachexia.
View Article and Find Full Text PDFJCO Oncol Pract
January 2025
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
Cachexia is a systemic wasting syndrome prevalent in patients with cancer that significantly affects quality of life, health care costs, and therapeutic outcomes. Despite its clinical importance, cachexia is rarely formally diagnosed. This deficiency presents a challenge for effective patient management and care, health care resource allocation, and the advancement of therapeutic approaches.
View Article and Find Full Text PDFUnlabelled: Cancer cachexia, a multifactorial condition resulting in muscle and adipose tissue wasting, reduces the quality of life of many people with cancer. Despite decades of research, therapeutic options for cancer cachexia remain limited. Cachexia is highly prevalent in people with pancreatic ductal adenocarcinoma (PDAC), and many animal models of pancreatic cancer are used to understand mechanisms underlying cachexia.
View Article and Find Full Text PDFHealth Sci Rev (Oxf)
December 2024
Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612 USA.
Introduction/background: An improved understanding of cancer-related cachexia and sarcopenia among patients with hematologic malignancies can improve their health outcomes. Patients with hematologic malignancies are affected by cancer-related cachexia and sarcopenia, but this aspect of their care is rarely studied. This review aims to increase awareness and knowledge of cancer-related cachexia and sarcopenia for patients with hematologic malignancies through a comprehensive synthesis of current research.
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