Hsiao 2016 Abstract MitoFit Science Camp 2016

From Bioblast
Jump to: navigation, search
Association between mitochondrial bioenergetics and radiation-related fatigue: a possible mechanism and novel target.
Link:
Chao-Pin Hsiao

Hsiao CP, Daly B, Hoppel CL (2016)

Event: MitoFit Science Camp 2016 Kuehtai AT

Fatigue is one of the cancer symptoms most often reported to nurses by patients receiving radiation therapy (XRT) [1]. With limited available options, novel strategies are needed to improve therapies for cancer-related fatigue. Understanding the mechanism behind the development of cancer-related fatigue will enable the design of novel interventions for radiation-induced fatigue. This project is designed to determine the relationships among mitochondrial genes, mitochondrial bioenergetics, and fatigue in prostate cancer patients receiving XRT.

We proposed a mechanism of mitochondrial bioenergetics for cancer-related fatigue based on a molecular-genetic approach, linking impaired ATP production as a consequence of XRT. Based on preliminary findings [2,3], we hypothesize that decreased BCS1L leads to a decrease of Rieske iron-sulfur protein incorporation into complex III. This incomplete complex III leads to a defect in complex III activity and causes impaired mitochondrial oxidative phosphorylation which results in decreased ATP production, contributing to fatigue.

This is a prospective, hypothesis testing project with a matched case-control, repeated-measures design. Two groups of subjects will be recruited-prostate cancer patients with localized XRT and prostate cancer patients without any treatment but under active surveillance. Peripheral blood will be collected from each subject at 3 timepoints (baseline, midpoint, and endpoint) to determine mitochondrial gene expression and mitochondrial bioenergetics profile. Fatigue will be measured using validated questionnaires [revised Piper Fatigue Scale (r-PFS) and Patient Reported Outcomes Measurement Information System for Fatigue (PROMIS-F)].

An increased fatigue score will be observed at midpoint of XRT and will remain elevated. Differentiated mitochondria-related genes (p < 0.05, > 2.0 fold change) and decreased mitochondrial bioenergetics profile will be detected in lymphocytes of prostate cancer patients receiving XRT at midpoint and endpoint of XRT. Furthermore, increased fatigue scores will be associated with differentiated genes and decreased mitochondrial bioenergetics in fatigued prostate cancer patients undergoing XRT.

Our hypothesis provides a mechanism for impaired ATP production as a major consequence of XRT that leads to debilitating radiation-induced fatigue.

The results have the potential to identify targets for pharmacological and, in particular, nutraceutical interventions and initiate a new direction for design of nursing interventions for cancer-related fatigue.

Keywords: Fatigue

O2k-Network Lab: US OH Cleveland Hoppel CL


Labels: MiParea: mt-Biogenesis;mt-density, mtDNA;mt-genetics, Patients  Pathology: Cancer 


Tissue;cell: Genital 

Enzyme: Complex III  Regulation: ATP production 


Event: B3, Poster  MitoFit Science Camp 2016 

Affiliations

1-Frances Payne Bolton School of Nursing; 2-School of Med, Case Western Reserve Univ; Cleveland, OH, USA. - cxh416@case.edu

References

  1. Berger AM, Mooney K, Alvarez-Perez A, Breitbart WS, Carpenter KM, Cella D, Cleeland C, Dotan E, Eisenberger MA, Escalante CP, Jacobsen PB, Jankowski C, LeBlanc T, Ligibel JA, Loggers ET, Mandrell B, Murphy BA, Palesh O, Pirl WF, Plaxe SC, Riba MB, Rugo HS, Salvador C, Wagner LI, Wagner-Johnston ND, Zachariah FJ, Bergman MA, Smith C; National comprehensive cancer network (2015) Cancer-related fatigue, Version 2.2015. J Natl Compr Canc Netw 13:1012-39.
  2. Hsiao CP, Wang D, Kaushal A, Chen MK, Saligan L (2014) Differential expression of genes related to mitochondrial biogenesis and bioenergetics in fatigued prostate cancer men receiving external beam radiation therapy. J Pain Symptom Manage 48:1080-90.
  3. Hsiao CP, Wang D, Kaushal A, Saligan L (2013) Mitochondria-related gene expression changes are associated with fatigue in patients with nonmetastatic prostate cancer receiving external beam radiation therapy. Cancer Nurs 36:189-97.