Many forms of cancer present with a complex metabolic profile characterised by loss of lean body mass known as cancer cachexia. The physical impact of cachexia contributes to decreased patient quality of life, treatment success and survival due to gross alterations in protein metabolism, increased oxidative stress and systemic inflammation. The psychological impact also contributes to decreased quality of life for both patients and their families. Combination therapies that target multiple pathways, such as eicosapentaenoic acid administered in combination with exercise, appetite stimulants, antioxidants or anti-inflammatories, have potential in the treatment of this complex syndrome and require further development.
Polyunsaturated fatty acids (PUFAs) derived from marine sources, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are widely consumed as supplements within the community. However, the use of marine PUFAs in a therapeutic context is also increasing in patients receiving treatment for a range of cancer types. On balance, the literature suggests that marine PUFAs have potential as an effective adjuvant to chemotherapy treatment, may have direct anticancer effects, and may help ameliorate some of the secondary complications associated with cancer. Although a range of doses have been trialled, it would appear that supplementation of fish oil (>3 g per day) or EPA/DHA (>1 g EPA and >0.8 g DHA per day) is associated with positive clinical outcomes. However, further research is still required to determine the mechanisms via which marine PUFAs are mediating their effects. This review summarises our current understanding of marine PUFAs and cancer therapy.
BackgroundCurrent research into the mechanisms of organ atrophy associated with cancer cachexia have centred on the loss of skeletal muscle, as it is one of the most profound physical changes of the disease. However, many patients with cancer cachexia also experience significant atrophy of the heart. The mechanisms causing cardiac tissue wastage in cancer cachexia are largely unknown. However, it is believed to involve a number of molecular interactions between the tumour and host. Increased levels of oxidative stress have been found in cancer cachectic skeletal muscle and has been linked to the activation of the ubiquitin proteosome system (UPS). The aim of the current study was to examine the role of oxidative stress and the UPS in the hearts of mice with cancer cachexia.MethodsOxidative damage to DNA (8-OH-2dG), mRNA levels of the ROS-producing enzymes NADPH oxidase (NOX), and xanthine oxidase (XDH), the antioxidant enzyme superoxide dismutase (SOD) and key components of the UPS was measured in the heart of mice with cancer cachexia. Protein expression levels of NOX enzyme subunits and SOD enzyme activity was also measured in the same heart samples.Results8-OH-2dG levels were 1.5-fold higher in the heart of mice with cancer cachexia, and this was associated with a 1.7-fold lower level of NOX2 mRNA and twofold higher XDH mRNA in the same hearts. Cancer cachexia was also associated with a 1.5-fold lower level of SOD activity in the heart. Accompanying these pro- and antioxidant differences was a significantly higher level of mRNA for the key UPS elements MURF-1 (4.3=fold) and MAFbx (3.8-fold) in the hearts of mice with cancer cachexia.ConclusionsThe current study demonstrated that cardiac atrophy of cachectic mice is associated with oxidative damage to DNA in the myocardium. The higher levels of XDH mRNA in cachectic hearts suggest that xanthine oxidase may have an important role to play in producing oxidative stress. It appears that the combination of higher XDH expression and lower SOD enzyme activity are key contributors to oxidative stress and cardiac tissue damage in cancer-induced cardiac atrophy. Oxidative stress in the myocardium as with skeletal muscle may also induce increased expression of the E3 ligases MURF-1 and MAFbx as seen in this study.Electronic supplementary materialThe online version of this article (doi:10.1007/s13539-013-0116-8) contains supplementary material.
Background Cancer cachexia (CC) is a debilitating syndrome severely impacting patients’ quality of life and survivorship. We aimed to investigate the health care professionals’ (HCPs’) experiences of dealing with CC. Methods Survey questions entailed definitions and guidelines, importance of CC management, clinician confidence and involvement, screening and assessment, interventions, psychosocial and food aspects. The online survey was disseminated through Australian and New Zealand palliative care, oncology, allied health and nursing organisations. Frequencies were reported using descriptive statistics accounting for response rates. Associations were examined between variables using Fisher’s exact and Pearson’s chi-square tests. Results Over 90% of the respondents (n = 192) were medical doctors or nurses. Over 85% of the respondents were not aware of any guidelines, with 83% considering ≥ 10% weight loss from baseline indicative of CC. CC management was considered important by 77% of HCPs, and 55% indicated that it was part of their clinical role to assess and treat CC. In contrast, 56% of respondents were not confident about managing CC, and 93% believed formal training in CC would benefit their clinical practice. Although formal screening tools were generally not used (79%), 75% of respondents asked patients about specific symptoms. Antiemetics (80%) and nutritional counselling (86%) were most prescribed or recommended interventions, respectively. Conclusion This study underlines the deficiencies in knowledge and training of CC which has implications for patients’ function, well-being and survival. HCP training and a structured approach to CC management is advocated for optimal and continued patient care.
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