Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise.
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2015-05
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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.
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Betof, Allison S, Christopher D Lascola, Douglas Weitzel, Chelsea Landon, Peter M Scarbrough, Gayathri R Devi, Gregory Palmer, Lee W Jones, et al. (2015). Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise. J Natl Cancer Inst, 107(5). 10.1093/jnci/djv040 Retrieved from https://hdl.handle.net/10161/12580.
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Scholars@Duke
Christopher David Lascola
Chelsea Dawn Landon
With a research background heavily weighted in drug delivery systems in the treatment of cancer, the focus of my work has shifted to vaccination delivery methods as potential anticancer strategies. The goal of my current funding is to identify and develop a vaccine strategy delivered via the intranasal (IN) route that induces a cytotoxic T lymphocyte (CTL) response adequate for the protection/prevention of metastatic lung cancer.
I am currently working under the mentorship of Dr. Herman Staats, and in addition to the cancer immunotherapy studies, I have a strong interest in mucosal immunization and maternal immunization studies, specifically in the rabbit model.
Gayathri R. Devi
Dr. Devi’s research interests include functional genomics, anti-cancer drug discovery and development, mechanisms of cancer cell signaling, tumor immunity and applications thereof for overcoming therapeutic resistance in cancer.
The lab has established prostate, inflammatory breast cancer and ovarian cellular and tumor models.
Gregory M. Palmer
Greg Palmer obtained his B.S. in Biomedical Engineering from Marquette University in 2000, after which he obtained his Ph.D. in BME from the University of Wisconsin, Madison. He is currently an Associate Professor in the Department of Radiation Oncology, Cancer Biology Division at Duke University Medical Center. His primary research focus has been identifying and exploiting the changes in absorption, scattering, and fluorescence properties of tissue associated with cancer progression and therapeutic response. To this end he has implemented a model-based approach for extracting absorber and scatterer properties from diffuse reflectance and fluorescence measurements. More recently he has developed quantitative imaging methodologies for intravital microscopy to characterize tumor functional and molecular response to radiation and chemotherapy. His awards have included the Jack Fowler Award from the Radiation Research Society.
Laboratory Website:
https://radonc.duke.edu/research-education/research-labs/radiation-and-cancer-biology/palmer-lab
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