Search

Background: Muscle wasting is a common phenomenon in oncology and seems to be attenuated by exercise training. The aim of this study is to determine the degree of aggressiveness of cancer-induced muscle wasting in two different phenotypic muscles. It will also determine whether exercise training can attenuate this muscle dysfunction. Methods: Fifty Sprague Dawley rats were randomly assigned to four experimental groups: two breast cancer model groups (sedentary and exercise) and two control groups (sedentary and exercise). Breast cancer was induced by 1-methyl-1-nitrosoureia (MNU). After 35 weeks of endurance training, animals were sacrificed, and gastrocnemius and soleus muscles harvested for morphometric analysis. Results: In sedentary tumor-bearing animals, a significant reduction in cross-sectional area was found in both muscles (p < 0.05). Interstitial fibrosis was significantly higher in the gastrocnemius muscle of the sedentary tumor-bearing animals (p < 0.05), but not in the soleus muscle. In the gastrocnemius of sedentary tumor-bearing animals, a shift from large to small fibers was observed. This cancer-related muscle dysfunction was prevented by long-term exercise training. Conclusions: In sedentary animals with tumors, the gastrocnemius muscle showed a very pronounced reduction in cross-sectional area and a marked degree of interstitial fibrosis. There was no difference in collagen deposition between tumor groups, and the soleus muscle showed a less pronounced but significant reduction in cross-sectional area. These contrasting results confirm that cancer-induced muscle wasting can affect specific types of fibers and specific muscles, namely fast glycolytic muscles, and that exercise training can be used to improve it. [ABSTRACT FROM AUTHOR]

Copyright of Applied Physiology, Nutrition & Metabolism is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this study was to investigate the temporal involvement of different proteolytic systems and muscle proteome changes during experimental disuse atrophy (up to 1 week hindlimb suspension, HS) in murine gastrocnemius muscle. The results showed that proteolysis, cytoprotection mechanisms and signs of cellular infiltration occurred very early. After 1 day of HS, signals of lysosomal activation, rather than programmed cell death (apoptosis), seem to trigger protein breakdown in the whole skeletal muscle. Moreover, the ubiquitin-proteasome pathway remained elevated later whereas all other proteolytic parameters returned to control values when atrophy was fully established. Using proteomics, evidence is provided for metabolic alterations toward glycolysis and for cytoskeleton remodelling suggestive of reduced capacity for force generation. Overall, our data highlight an early and coordinated time-dependent activation of proteolysis, which explains the global proteome alterations observed in gastrocnemius under atrophic conditions. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate the mechanisms of cell death (apoptosis vs. necrosis) during muscle atrophy induced by 1 week of hindlimb suspension. Biochemical and morphological parameters were examined in murine soleus and gastrocnemius muscles. A total of 70 male Charles River CD1 mice were randomly assigned to seven groups (n = 10/group): Cont (loading control conditions) and 6HS, 12HS, 24HS, 48HS, 72HS and 1wkHS with respect to the period of hindlimb suspension (HS). Compared to the Cont, skeletal muscle atrophy was confirmed by a significant decrease of 44 and of 17% in fiber cross-sectional areas in the gastrocnemius and soleus, respectively. A significant increase in caspase-3 activity was noticed in 6HS (196%, P < 0.05) and in 12HS (201%, P < 0.05), as well as the amount of cytosolic mono- and oligonucleosomes at 12HS (142%, P < 0.05) and 24HS (203%, P < 0.05) in the gastrocnemius and soleus, respectively. The profile of necrotic markers showed a peak of myeloperoxidase activity at 24HS (170%, P < 0.05) and at 72HS (114%, P < 0.05) in the gastrocnemius and soleus, respectively. The analysis of N-acetylglucosaminidase activity evidenced more increment in the soleus at 72HS (60%, P < 0.05). The analysis of the basal values of these parameters suggested that apoptosis prevailed in the slow-twitch muscle analyzed, whereas lysosomic activity seemed to be more pronounced in the gastrocnemius. The morphological data supported the biochemical results pointing towards a shift from apoptosis to necrosis, which seems to corroborate the aponecrosis theory. [ABSTRACT FROM AUTHOR]

The comprehension of the cellular mechanisms underlying skeletal muscle atrophy has been the aim of several experimental studies. However, the majority of them focused on alterations of the myocytes induced by different experimental conditions yet disregarding the contribution of other cells such as endothelial cells and fibroblasts. In this sense, 70 Charles River CD1 male mice were randomly assigned to seven groups (n=10 per group): control and 6, 12, 24, 48, 72 h and 1 week with respect to the period of hindlimb suspension. Forty-eight hours before sacrifice, the animals were injected with bromodeoxyuridine (BrdU) in order to identify proliferating cells. Immunohistochemistry and south-western blotting techniques were used to evaluate across the whole gastrocnemius muscle BrdU incorporation into the different proliferating cells. The contribution of the apoptotic response was also measured in order to ascertain whether the balance between cell survival and death was preserved. The results observed during 1 week of unloading-induced atrophy evidenced an intense peak of proliferating activity only after 6 h, mainly due to the duplication of satellite cells. Consequently to this unexpected activation of satellite cells, the addition of nuclei to the fibre syncytium was recognized at 12 h of unloading. After 48 h of weightlessness, the proliferating activity observed was largely due to an interstitial fibrosis. According to the apoptotic index profile observed during the analysed unloading period, this general proliferative activity was balanced by apoptosis, which strongly suggests the existence of a regulatory feedback response between anabolic and catabolic events in unloading-induced skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

Purpose: Although resistance exercise (RE) is now recognized as an adjuvant in cancer treatment because of its capacity to prevent muscle wasting, weakness, and cachexia, it is unknown whether RE can mitigate tumor development. Two solid adenocarcinoma models (Walker-256 and Ehrlich) were used to investigate the effects of RE on tumor cell proliferation, growth, and aggressiveness parameters in tumor-bearing animals' life span. Methods: Walker-256 tumor-bearing rats and Ehrlich tumor-bearing mice were subjected to RE, which consisted of climbing a ladder apparatus with loads tied to their tails. After 4 wk, animals were euthanized, and tumors were excised and assessed for tumor microenvironment evaluation such as cell proliferation and apoptosis determination, collagen deposit, and presence of malignant tumor morphology. Results: Our data demonstrate that RE mitigated tumor growth and favored tumor end points such as lower Scarff–Bloom–Richardson histological grade tumor, denoting slow cell aberrant form and division, decreased tumor cell proliferation (evaluated by nucleus marked with antigen ki-67), and lower viable tumor area in both types of tumors studied. In addition, RE stimulated tumor microvessel density in Walker-256 tumor-bearing rats, but there was no change in their life span. Conclusion: RE may mitigate tumor growth and tumor malignancy parameters such as lower histopathological grade, assuming less nuclear pleomorphism and mitotic cells, smaller viable tumor area, and decreased tumor cell proliferation in both adenocarcinomas. In addition, RE induced tumor vascularization. [ABSTRACT FROM AUTHOR]