Graduation Date

Spring 5-9-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Nursing

First Advisor

Paula Schulz, Ph.D.

Second Advisor

Leorey Saligan, Ph.D.

Third Advisor

Leonid Margolis, Ph.D.

Fourth Advisor

Ann Berger, Ph.D.

Abstract

Cancer survivors report many debilitating symptoms associated with cancer and its treatments. About 30% will report long-term cancer-related fatigue (CRF) which often co-occurs with depressive symptoms, sleep disturbances, cognitive fatigue, and poor overall health-related quality of life. The underlying causes of these co-occurring symptoms have been related to systemic processes such as inflammation. Extracellular vesicles (EVs) contain systemic markers such as genetic and protein materials that inform about cell-to-cell interactions that influence immune signaling and inflammatory processing. No study to date has explored the associations of EVs with cancer-related symptoms. So, the purpose of this dissertation was to investigate the associations of EVs and EV-associated markers with CRF and its co-occurring symptoms. Six questionnaires to assess symptoms were administered and plasma samples were collected for biomarker analyses. Western blot, transmission electron microscopy, and NanoSight characterized the EVs, and bead-based assays detected the inflammatory and neurotrophic markers. The dissertation write-up includes three manuscripts. Manuscript I is a systematic review examining the effects of yoga on inflammatory biomarkers in chronic inflammatory conditions such as cancer, heart disease, rheumatoid arthritis, and chronic stress. Manuscript II explored the relationships of CRF and EV- associated and soluble markers in men with non-metastatic cancer (n=40) at the start and at three months post external beam radiation therapy (EBRT). This manuscript revealed that EV-associated markers significantly correlated with CRF scores, corroborating previously identified markers in a similar cohort. Manuscript III explored the associations of EV-associated markers with CRF and its co-occurring symptoms in EBRT men (n=40) compared to men on active surveillance (n=20). Findings showed that co-occurring symptoms were significantly associated with CRF in both AS and EBRT men, particularly at three months post EBRT. Worsening symptoms were associated with EV-associated inflammatory markers. These findings offer implications for future practice and research. EVs may serve as potential early biomarkers for cancer-related symptoms. Future research will identify cell origins of these EV-associated inflammatory markers that correlated with worsening cancer-related symptoms.

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