caa a22 4500 445298685 CHVBK 20180317142550.0 cr unu---uuuuu 170323e20101201xx s 000 0 eng 10.1007/s11864-010-0127-z doi (NATIONALLICENCE)springer-10.1007/s11864-010-0127-z Cancer Cachexia: Traditional Therapies and Novel Molecular Mechanism-Based Approaches to Treatment [Elektronische Daten] [Nagi Kumar, Aslam Kazi, Tiffany Smith, Theresa Crocker, Daohai Yu, Richard Reich, Kiran Reddy, Sally Hastings, Martine Exterman, Lodovico Balducci, Kyle Dalton, Gerold Bepler] Opinion statement: The complex syndrome of cancer cachexia (CC) that occurs in 50% to 80% cancer patients has been identified as an independent predictor of shorter survival and increased risk of treatment failure and toxicity, contributing to the mortality and morbidity in this population. CC is a pathological state including a symptom cluster of loss of muscle (skeletal and visceral) and fat, manifested in the cardinal feature of emaciation, weakness affecting functional status, impaired immune system, and metabolic dysfunction. The most prominent feature of CC is its non-responsiveness to traditional treatment approaches; randomized clinical trials with appetite stimulants, 5-HT3 antagonists, nutrient supplementation, and Cox-2 inhibitors all have failed to demonstrate success in reversing the metabolic abnormalities seen in CC. Interventions based on a clear understanding of the mechanism of CC, using validated markers relevant to the underlying metabolic abnormalities implicated in CC are much needed. Although the etiopathogenesis of CC is poorly understood, studies have proposed that NFkB is upregulated in CC, modulating immune and inflammatory responses induce the cellular breakdown of muscle, resulting in sarcopenia. Several recent laboratory studies have shown that n-3 fatty acid may attenuate protein degradation, potentially by preventing NFkB accumulation in the nucleus, preventing the degradation of muscle proteins. However, clinical trials to date have produced mixed results potentially attributed to timing of interventions (end stage) and utilizing outcome markers such as weight which is confounded by hydration, cytotoxic therapies, and serum cytokines. We propose that selective targeting of proteasome activity with a standardized dose of omega-3-acid ethyl esters, administered to cancer patients diagnosed with early stage CC, in addition to a standard intervention with nutritionally adequate diet and appetite stimulants, will alter metabolic abnormalities by downregulating NFkB, preventing the breakdown of myofibrillar proteins and resulting in increasing serum protein markers, lean body mass, and functional status. The Author(s), 2010 Kumar Nagi Department of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, 12902 Magnolia Drive, 33612, Tampa, FL, USA aut Kazi Aslam Department of Drug Discovery, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut Smith Tiffany Department of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, 12902 Magnolia Drive, 33612, Tampa, FL, USA aut Crocker Theresa Department of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, 12902 Magnolia Drive, 33612, Tampa, FL, USA aut Yu Daohai Department of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut Reich Richard Department of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut Reddy Kiran Martin Memorial Hospital, Moffitt Affiliate Network, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut Hastings Sally Martin Memorial Hospital, Moffitt Affiliate Network, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut Exterman Martine Department of Experimental Therapeutics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut Balducci Lodovico Department of Experimental Therapeutics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut Dalton Kyle Department of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, 12902 Magnolia Drive, 33612, Tampa, FL, USA aut Bepler Gerold Department of Experimental Therapeutics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut Current Treatment Options in Oncology Springer US; http://www.springer-ny.com 11/3-4(2010-12-01), 107-117 1527-2729 11:3-4<107 2010 11 11864 https://doi.org/10.1007/s11864-010-0127-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11864-010-0127-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kumar Nagi Department of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, 12902 Magnolia Drive, 33612, Tampa, FL, USA aut NATIONALLICENCE 700 1- Kazi Aslam Department of Drug Discovery, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut NATIONALLICENCE 700 1- Smith Tiffany Department of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, 12902 Magnolia Drive, 33612, Tampa, FL, USA aut NATIONALLICENCE 700 1- Crocker Theresa Department of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, 12902 Magnolia Drive, 33612, Tampa, FL, USA aut NATIONALLICENCE 700 1- Yu Daohai Department of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut NATIONALLICENCE 700 1- Reich Richard Department of Biostatistics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut NATIONALLICENCE 700 1- Reddy Kiran Martin Memorial Hospital, Moffitt Affiliate Network, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut NATIONALLICENCE 700 1- Hastings Sally Martin Memorial Hospital, Moffitt Affiliate Network, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut NATIONALLICENCE 700 1- Exterman Martine Department of Experimental Therapeutics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut NATIONALLICENCE 700 1- Balducci Lodovico Department of Experimental Therapeutics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut NATIONALLICENCE 700 1- Dalton Kyle Department of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, 12902 Magnolia Drive, 33612, Tampa, FL, USA aut NATIONALLICENCE 700 1- Bepler Gerold Department of Experimental Therapeutics, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida College of Medicine, Tampa, FL, USA aut NATIONALLICENCE 773 0- Current Treatment Options in Oncology Springer US; http://www.springer-ny.com 11/3-4(2010-12-01), 107-117 1527-2729 11:3-4<107 2010 11 11864 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer