Date of Graduation

7-2021

Document Type

Thesis

Degree Name

Master of Science in Cell & Molecular Biology (MS)

Degree Level

Graduate

Department

Biological Sciences

Advisor

Nicholas P. Greene

Committee Member

Tyrone A. Washington

Second Committee Member

Timothy J. Muldoon

Keywords

cachexia, cancer, kinesiology, mitochondria, muscle

Abstract

Cachexia is a multisystemic and multifactorial syndrome prevalent in cancer patients. It is clinically defined by involuntary loss of >5% weight in a six-month window, despite nutritional interventions. A negative energy balance characterizes cancer cachexia (CC), it is associated with weakness and fatigue in skeletal muscle. Impaired muscle function is associated with lower quality of life in cancer patients. Defects in mitochondrial function are strongly associated with muscle wasting. This study explored muscular contractile function and mitochondrial quality control (MQC) markers in soleus, gastrocnemius, and tibialis anterior (TA) muscles of C26-induced male tumor-bearing mice during a 25-day time course. It was demonstrated that C26 colorectal cancer induces skeletal muscle atrophy aggravated as it develops, with a reduction up to 15% in body weight, affecting all the mentioned tissues. Higher fatigue is present after 25 days of tumor development, and an overall decrease in the isometric force could be seen starting after 10 days. Opa1, Fis1, Bnip3, Lonp1, and Parl1 mRNA content was measured in the three tissues, with a lower content of Opa1 in TA and a greater increased Bnip3 content on gastrocnemius after 25 days. No significant differences were observed in Fis1, Lonp1, or Parl1 25 days following tumor allograft compared to PBS control. In conclusion, this study showed the induction of CC by C26 colon carcinoma, associated with a decrease in muscle force and higher fatigue with intrinsic differences in the mitochondrial metabolism and heterogenicity of different muscle responses to CC in males.

Available for download on Sunday, September 10, 2023

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