| Autor: |
Choi E; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts ; Deparment of Physical Medicine and Rehabilitation, Hallym University College of Medicine Gangwon-do, South Korea., Carruthers K; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts., Zhang L; Forsyth Institute Cambridge, Massachusetts., Thomas N; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts., Battaglino RA; Forsyth Institute Cambridge, Massachusetts., Morse LR; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts ; Forsyth Institute Cambridge, Massachusetts., Widrick JJ; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts. |
| Abstrakt: |
Cachexia is defined as an excessive, involuntary loss of fat and lean tissue. We tested the validity of the Lewis lung carcinoma (LLC) as a model of cancer cachexia and examined its effect on the two major lean tissue components, skeletal muscle and bone. LLC cells (0.75 × 10(6)) were injected into the left thigh of C57BL/6 mice. Control mice received an equal volume injection of growth media. Tumors were observed in all LLC-injected animals 21 and 25 days post inoculation. LLC-injected animals showed significant reductions in fat and lean mass despite having the same average daily caloric intake as media-treated mice. Global bone mineral density (BMD) had fallen by 5% and 6% in the LLC animals at 21 and 25 days, respectively, compared to a BMD increase of 5% in the 25-day media-treated animals. Extensor digitorum longus (EDL) muscles (isolated from the noninjected hindlimb) showed earlier and quantitatively greater losses in mass, physiological cross-sectional area (pCSA), and tetanic force compared to soleus muscles from the same hindlimb. By the 25th day post-LLC inoculation, EDL force/pCSA was reduced by 19% versus media treatment. This loss in specific force was not trivial as it accounted for about one-third of the reduction in EDL absolute force at this time point. Muscle strips dissected from the diaphragm of LLC mice also exhibited significant reductions in force/pCSA at day 25. We conclude that LLC is a valid model of cachexia that induces rapid losses in global BMD and in limb and respiratory muscle function. |
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