Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia.

作者: K. T. Murphy , A. Chee , J. Trieu , T. Naim , G. S. Lynch

DOI: 10.1242/DMM.008839

关键词:

摘要: Cancer cachexia describes the progressive skeletal muscle wasting and weakness that is associated with many cancers. It impairs quality of life accounts for >20% all cancer-related deaths. The main outcome affects mortality loss function so preclinical models should exhibit similar functional impairments in order to maximize translational outcomes. Mice bearing colon-26 (C-26) tumors are commonly used cancer studies but few have provided comprehensive assessments physiological metabolic impairment, especially those factors impact life. Our aim was characterize mildly severely affected cachectic mice, determine suitability these mice as a model. Metabolic abnormalities also evident patients we investigated whether C-26-tumor-bearing had aberrations. Twelve-week-old CD2F1 received subcutaneous injection PBS (control) or C-26 tumor cells. After 18–20 days, were made grip strength, rotarod performance, locomotor activity, whole body metabolism, contractile properties tibialis anterior (TA) muscles (in situ) diaphragm strips vitro). Injection cells reduced mass, epididymal fat mass. exhibited lower strength performance. Locomotor activity impaired following injection, reductions movement distance, duration speed compared controls. TA from maximum force (−27%) more susceptible fatigue. Maximum specific (normalized) (−10%) during fatiguing stimulation lower. carbohydrate oxidation increased range consistency confirm their model cachexia. We recommend use translation findings accurately identify effective treatments

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