Anorexia, inflammation, insulin resistance and increased muscle protein breakdown are frequently associated with cachexia. The prominent clinical feature of cachexia is weight loss. 3, 4 In 2008 a consensus, 5 defined cachexia as aĬomplex metabolic syndrome associated with underlying illness and characterised by loss of muscle with or without loss of fat mass. 1 Moreover, cachexia is linked with a decrease in physical activity 2 and results in a poor quality of life and a decreased efficacy and outcome of antitumoural treatment. Cachexia is responsible for more than 20% of cancer deaths in humans. The percentage of cancer patients affected by cachexia varies from 50 to 80% constituting a useful survival estimate.
Keywords: cancer cachexia, skeletal muscle, dantrolene, formoterol, calcium, ryanodine receptor 1 Finally, the combined treatment (formoterol and dantrolene) did not result in any significant benefit on the action of the β 2-agonist.Ĭonclusion: It is concluded that, in the preclinical cachectic model used, no synergy exists between β 2-agonist treatment and the blockade of sarcoplasmic-calcium flow. Results: While formoterol had, as in previous studies, a very positive effect in reducing muscle weight loss, dantrolene had no effects, neither on skeletal muscle nor on any of the parameters studied.
7 days after tumour transplantation, muscle weight, grip force, and total physical activity were specified in all experimental groups.
TB group was further subdivided into four groups: untreated (saline as a vehicle), treated with Formoterol (TF) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with Dantrolene (TD) (5 mg/kg body weight in saline, subcutaneous (s.c.), daily), and double-treated treated (TFD) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and Dantrolene (5 mg/kg body weight, subcutaneous (s.c.), daily). Methods: Rats were separated into two groups: controls (C) and tumour bearing (TB). The object of the present research was to study the effects of a combination of formoterol and dantrolene, an inhibitor of the ryanodine receptor 1 (RyR1), on body weight loss and cachexia in tumour-bearing animals. The use of β 2-agonists, formoterol in particular, has proven to be very successful in the treatment of the syndrome in pre-clinical models. Silvia Busquets, 1, 2 Marta Castillejo, 1 Queralt Jové, 1 Baptiste Jude, 3 Patricia Mejías, 1 Francisco J López-Soriano, 1, 2 Josep M Argilés 1, 2ġCancer Research Group, Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain 2Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain 3Laboratoire de Physiologie - EA 4324 ORPHY, IBSAM, Université de Bretagne Occidentale, Brest, FranceĬancer Research Group, Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 643, Barcelona, 08028, Spainīackground: During cancer cachexia, both skeletal muscle and adipose tissue losses take place.
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