Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise.

Betof, Allison S

Lascola, Christopher D

Weitzel, Douglas

Landon, Chelsea

Scarbrough, Peter M

Devi, Gayathri R

Palmer, Gregory

Jones, Lee W

Dewhirst, Mark W

United States

2016-08-02T17:37:41Z

2015-05

Exercise has been shown to improve postischemia perfusion of normal tissues; we investigated whether these effects extend to solid tumors. Estrogen receptor-negative (ER-, 4T1) and ER+ (E0771) tumor cells were implanted orthotopically into syngeneic mice (BALB/c, N = 11-12 per group) randomly assigned to exercise or sedentary control. Tumor growth, perfusion, hypoxia, and components of the angiogenic and apoptotic cascades were assessed by MRI, immunohistochemistry, western blotting, and quantitative polymerase chain reaction and analyzed with one-way and repeated measures analysis of variance and linear regression. All statistical tests were two-sided. Exercise statistically significantly reduced tumor growth and was associated with a 1.4-fold increase in apoptosis (sedentary vs exercise: 1544 cells/mm(2), 95% CI = 1223 to 1865 vs 2168 cells/mm(2), 95% CI = 1620 to 2717; P = .048), increased microvessel density (P = .004), vessel maturity (P = .006) and perfusion, and reduced intratumoral hypoxia (P = .012), compared with sedentary controls. We also tested whether exercise could improve chemotherapy (cyclophosphamide) efficacy. Exercise plus chemotherapy prolonged growth delay compared with chemotherapy alone (P < .001) in the orthotopic 4T1 model (n = 17 per group). Exercise is a potential novel adjuvant treatment of breast cancer.

http://www.ncbi.nlm.nih.gov/pubmed/25780062

djv040

1460-2105

https://hdl.handle.net/10161/12580

eng

Oxford University Press (OUP)

J Natl Cancer Inst

10.1093/jnci/djv040

Analysis of Variance

Animals

Antineoplastic Agents, Alkylating

Apoptosis

Cell Hypoxia

Cell Line, Tumor

Cell Proliferation

Cyclophosphamide

Exercise

Female

Humans

Linear Models

Mammary Neoplasms, Experimental

Mice

Mice, Inbred BALB C

Microcirculation

Neoplasm Transplantation

Neovascularization, Pathologic

Random Allocation

Receptors, Estrogen

Treatment Outcome

Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise.

Journal article

Lascola, Christopher D|0000-0002-8031-782X

Devi, Gayathri R|0000-0001-9158-7289

Palmer, Gregory|0000-0003-2955-8297

Dewhirst, Mark W|0000-0003-3459-6546

http://www.ncbi.nlm.nih.gov/pubmed/25780062

5

Basic Science Departments

Biomedical Engineering

Clinical Science Departments

Duke

Duke Cancer Institute

Duke-UNC Center for Brain Imaging and Analysis

Institutes and Centers

Neurobiology

Pathology

Pratt School of Engineering

Radiation Oncology

Radiology

Radiology, Neuroradiology

School of Medicine

Surgery

Surgery, Surgical Sciences

Published online

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