Differential response to exercise in claudin-low breast cancer

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2017-01-01

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Abstract

© Glass et al. Exposure to exercise following a breast cancer diagnosis is associated with reductions in the risk of recurrence. However, it is not known whether breast cancers within the same molecular-intrinsic subtype respond differently to exercise. Syngeneic mouse models of claudin-low breast cancer (i.e., EO771, 4TO7, and C3(1)SV40Tagp16- luc) were allocated to a uniform endurance exercise treatment dose (forced treadmill exercise) or sham-exercise (stationary treadmill). Compared to shamcontrols, endurance exercise treatment differentially affected tumor growth rate: 1- slowed (EO771), 2- accelerated (C3(1)SV40Tag-p16-luc), or 3- was not affected (4TO7). Differential sensitivity of the three tumor lines to exercise was paralleled by effects on intratumoral Ki-67, Hif1-a, and metabolic programming. Inhibition of Hif1-α synthesis by the cardiac glycoside, digoxin, completely abrogated exerciseaccelerated tumor growth in C3(1)SV40Tag-p16-luc. These results suggest that intratumoral Hif1-α expression is an important determinant of claudin-low breast cancer adaptation to exercise treatment.

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10.18632/oncotarget.21054

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Glass, OK, M Bowie, J Fuller, D Darr, JU sary, K Boss, KR Choudhury, X Liu, et al. (2017). Differential response to exercise in claudin-low breast cancer. Oncotarget, 8(60). pp. 100989–101004. 10.18632/oncotarget.21054 Retrieved from https://hdl.handle.net/10161/15836.

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Scholars@Duke

Glass

Oliver Kent Glass

Adjunct Assistant Professor in the Department of Medicine

My research interests are understanding how and why exercise is effective in chronic disease. I am interested in the unique role of skeletal muscle as a key mediator of exercise effects. 

Dewhirst

Mark Wesley Dewhirst

Gustavo S. Montana Distinguished Professor Emeritus of Radiation Oncology

Mark W. Dewhirst, DVM, PhD is the Gustavo S. Montana Professor of Radiation Oncology and Vice Director for Basic Science in the Duke Cancer Institute. Dr. Dewhirst has research interests in tumor hypoxia, angiogenesis, hyperthermia and drug transport. He has spent 30 years studying causes of tumor hypoxia and the use of hyperthermia to treat cancer. In collaboration with Professor David Needham in the Pratt School of Engineering, he has developed a novel thermally sensitive drug carrying liposome that has been successfully translated to human clinical trials. He has utilized the thermal characteristics of this liposome to develop an MR imageable form that can accurately reflect drug concentrations in tumors, which then is related to the extent of anti-tumor effect in pre-clinical models. This property has been widely used by other investigators, world-wide, particularly in the area of high intensity focused ultrasound, where it would be possible to literally paint drug to a target zone and visualize this process in real time, during heating. For his work in this area, Dr. Dewhirst was named a Fellow in the AAAS. Dr. Dewhirst has well over 500 peer-reviewed publications, book chapters and reviews, with >20,000 citations and an H-index of 73. He has given named lectures at the University of Western Ontario, Thomas Jefferson University and the New Zealand Cancer Society. He was awarded the Failla Medal and Lecture at the Radiation Research Society in 2008, the Eugene Robinson award for excellence hyperthermia research in 1992 and a similar award from the European Society for Hyperthermic Oncology in 2009. He was named a fellow of ASTRO in 2009 and was awarded the prestigious Gold Medal from the same society in 2012. He is a Senior Editor of Cancer Research and Editor-in-Chief of the International Journal of Hyperthermia. He has mentored 24 graduate students, and many postdoctoral fellows, residents, junior faculty and medical students. He has been particularly skillful in assisting those he has mentored to obtain DOD and NIH fellowships, K awards and first R01 grants. His skill in mentoring has been recognized by the Duke Comprehensive Cancer Center, the Medical Physics Graduate Training programs and the School of Medicine, where he has received “Mentor of the Year” awards. In 2011 he was selected to become the first Associate Dean of Faculty Mentoring in the Duke School of Medicine. In this position, he is implementing a comprehensive program to enhance success in obtaining NIH funding. He graduated from the University of Arizona in 1971 with a degree in Chemistry and Colorado State University in 1975 and 1979 with DVM and PhD degrees, respectively.


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