Date of Graduation

5-2020

Document Type

Thesis

Degree Name

Master of Science in Kinesiology (MS)

Degree Level

Graduate

Department

Health, Human Performance and Recreation

Advisor/Mentor

Greene, Nicholas P.

Committee Member

Washington, Tyrone A.

Second Committee Member

McDermott, Brendon P.

Keywords

Cachectic; Cancer; Cancer Cachexia; Female Tumor Bearing Mice; Lewis lung Carcinoma; Protein Degradation

Abstract

Background: Cancer is a leading cause of death in the world in which half of the people affected by this disease die from its effects. Cancer-cachexia is a syndrome associated with the significant loss of skeletal muscle mass and function, which cannot be fully reversed by nutritional intervention alone and in turn, impairs the host. Cancer-cachexia affects 50-80% of cancer patients and is a primary cause of death accounting for 20-40% of cancer related deaths. Efforts to reverse the effects of cancer-related cachexia have been largely unsuccessful and have primarily focused on the late stages of CC. Methods: Lewis Lung Carcinoma (LLC) was injected into C57BL6/J mice into their hind flank at 8 weeks of age. The tumor was allowed to develop for a LT and HT group and was compared to a PBS control. Results: Tumor weight was significantly higher in HT mice in comparison to LT mice. Gastrocnemius and plantaris weight in LT and HT in comparison to PBS mice was lower than LT. The soleus was lower in weight in HT mice when compared to PBS mice. TA mass was significantly lower in HT mice when compared to PBS mice. Spleen mass was significantly higher. Fat weight was significantly lower in HT mice when compared to PBS. Atrogin-1 was significantly higher in HT mice when compared to PBS mice. MuRF-1 in HT mice was significantly greater than PBS mice. Ubiquitin HT was significantly greater when compared to PBS and greater than LT. IL-6 was significantly higher in HT mice when compared to PBS mice. Progesterone levels were significantly lower in HT and LT mice when compared to PBS mice. Estrogen levels were significantly lower in HT and LT mice when compared to PBS mice. Conclusions: There appears to be a protective nature in the role of estrogen and progesterone and a negative relationship between these hormones and muscle atrophy. Levels of the E3 ligases Atrogin-1 and MuRF-1 may be elevated in the absence and presence of atrophying muscle and are significantly elevated in atrophic female LLC mice.

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