On the possible role of PIF in myofibrillar proteins mobilisation from skeletal muscles in the presence of non-malignant foci of growth in organism

Rapoport, E. A.

doi:10.1038/sj.bjc.6604116

Cited by 1 publication

(1 citation statement)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the etiopathogenesis of CC is poorly understood, multiple biologic pathways are known to be involved, including pro-inflammatory cytokines [ 6 – 8 ], neuroendocrine hormones [ 4 , 9 •], downregulation of IGF-1 [ 2 •] and tumor-specific factors such as proteolysis inducing factor (PIF) [ 10 , 11 ••]. Cytokines that are important in the initiation of the acute phase response (APR) have also been hypothesized in the genesis of CC [ 12 ••, 13 •] or the result rather than the cause of CC.…”

Section: Introductionmentioning

confidence: 99%

Cancer Cachexia: Traditional Therapies and Novel Molecular Mechanism-Based Approaches to Treatment

Kumar

Kazi

Smith

et al. 2010

Curr. Treat. Options in Oncol.

103

View full text Add to dashboard Cite

Opinion statementThe 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.

show abstract