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      Cancer cachexia: impact, mechanisms and emerging treatments

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          Abstract

          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.

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          Most cited references178

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          Cachexia in cancer patients.

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            Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis.

            Cancer cachexia is a multifactorial syndrome that is poorly defined. Our objective was to evaluate whether a 3-factor profile incorporating weight loss (> or = 10%), low food intake ( or = 10 mg/L) might relate better to the adverse functional aspects of cachexia and to a patient's overall prognosis than will weight loss alone. One hundred seventy weight-losing (> or = 5%) patients with advanced pancreatic cancer were screened for nutritional status, functional status, performance score, health status, and quality of life. Patients were followed for a minimum of 6 mo, and survival was noted. Patients were characterized by using the individual factors, > or = 2 factors, or all 3 factors. Weight loss alone did not define a population that differed in functional aspects of self-reported quality of life or health status and differed only in objective factors of physical function. The 3-factor profile identified both reduced subjective and objective function. In the overall population, the 3 factors, > or = 2 factors, and individual profile factors (except weight loss) all carried adverse prognostic significance (P < 0.01). Subgroup analysis showed that the 3-factor profile carried adverse prognostic significance in localized (hazard ratio: 4.9; P < 0.001) but not in metastatic disease. Weight loss alone does not identify the full effect of cachexia on physical function and is not a prognostic variable. The 3-factor profile (weight loss, reduced food intake, and systemic inflammation) identifies patients with both adverse function and prognosis. Shortened survival applies particularly to cachectic patients with localized disease, thereby reinforcing the need for early intervention.
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              Ubiquitylation in innate and adaptive immunity.

              Protein ubiquitylation has emerged as a key mechanism that regulates immune responses. Much like phosphorylation, ubiquitylation is a reversible covalent modification that regulates the stability, activity and localization of target proteins. As such, ubiquitylation regulates the development of the immune system and many phases of the immune response, including its initiation, propagation and termination. Recent work has shown that several ubiquitin ligases help to prevent the immune system from attacking self tissues. The dysfunction of several ubiquitin ligases has been linked to autoimmune diseases.
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                Author and article information

                Contributors
                +61-3-52271111 , +61-3-52272945 , paul.lewandowski@deakin.edu.au
                Journal
                J Cachexia Sarcopenia Muscle
                J Cachexia Sarcopenia Muscle
                Journal of Cachexia, Sarcopenia and Muscle
                Springer-Verlag (Berlin/Heidelberg )
                2190-5991
                2190-6009
                25 October 2012
                June 2013
                : 4
                : 2
                : 95-109
                Affiliations
                [ ]School of Medicine, Deakin University, 75 Pigdons Road, Waurn Ponds, Victoria 3216 Australia
                [ ]Palliative Care Program, Barwon Health, Geelong, Victoria Australia
                Article
                87
                10.1007/s13539-012-0087-1
                3684701
                23097000
                43943fb9-f90c-4341-9cf2-01909fe67bd3
                © Springer-Verlag 2012
                History
                : 15 February 2012
                : 3 September 2012
                Categories
                Review
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2013

                Orthopedics
                cancer cachexia,oxidative stress,antioxidant,eicosapentaenoic acid,oxypurinol
                Orthopedics
                cancer cachexia, oxidative stress, antioxidant, eicosapentaenoic acid, oxypurinol

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