Date of Graduation

5-2017

Document Type

Thesis

Degree Name

Bachelor of Science

Degree Level

Undergraduate

Department

Health, Human Performance and Recreation

Advisor

Greene, Nicholas

Reader

Washington, Tyrone

Second Reader

McDermott, Brendon

Abstract

Cancer is one of the leading causes of death across the world. Cancer-cachexia is a serious complication induced by cancer resulting in whole body muscle wasting and is responsible for up to 40% of cancer related deaths. Underlying mechanisms of cancer-cachexia are not well understood; however, a loss in oxidative metabolism in skeletal muscle is apparent in cancer-cachexia. PURPOSE: To examine oxidative phenotype of skeletal muscle in tumor bearing mice during progression of cancer-cachexia. METHODS: Mice were implanted with Lewis Lung Carcinoma (LLC) or sham phosphate buffered saline (PBS) at 8 weeks of age. The tumor was allowed to progress for four weeks, with cohorts harvested weekly. Tibialis Anterior (TA) muscle cross sections were stained for Succinate dehydrogenase (SDH) to analyze the percent of oxidative muscle fibers and cross-sectional area (CSA) of SDH positive and negative fibers was analyzed. Immunoblotting was utilized to examine markers of mitochondrial content and biogenesis, specifically peroxisome proliferator-activated receptor- γ coactivator-1α (PGC-1α) and Cytochrome c oxidase-IV (COX-IV). RESULTS: TA weight was approximately 10% lower in 4 week LLC mice when compared to PBS control mice. In the PBS group, 65% of fibers were SDH positive compared to only 40% SDH positive in 4 week LLC mice with no other differences among groups. COX-IV was significantly reduced in 4 week LLC mice compared to PBS with no other differences among groups. No significant differences in PGC-1α were observed. CONCLUSION: LLC in mice may promote a cellular energy crisis leading to a decrease in skeletal muscle oxidative phenotype. Based on my findings, promoting the oxidative phenotype and hence the mitochondrial network could be a potential therapeutic target to treat cancer-cachexia.

Available for download on Thursday, October 25, 2018

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