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Center for Energy Balance in Cancer Prevention &amp; Survivorship, Duncan Family Institute for Cancer Prevention and Risk Assessment 2. Knox Family Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The efficacy of chemotherapy is reduced by dysfunctional tumor vasculature, which may limit chemotherapy delivery to tumors. Preclinical studies have shown that moderate aerobic exercise improves tumor vascular function and increases chemotherapy efficacy in mouse models, but the effect of exercise on human tumor vasculature has not yet been determined. Here, we demonstrate that exercise remodels the tumor vasculature, accelerates the regression, and delays the regrowth of pancreatic ductal adenocarcinoma in a patient-derived xenograft mouse model treated with gemcitabine. By evaluating pancreatic adenocarcinoma specimens from patients treated with preoperative chemotherapy or chemoradiation therapy, we also demonstrate for the first time that tumor vascular remodeling occurs in association with exercise in humans. Future studies will evaluate whether exercise-induced vascular remodeling improves gemcitabine or other chemotherapy efficacy in patients, as this study evaluated only changes in tumor vascular structure.<\/jats:p>","DOI":"10.1038\/s41598-019-49582-3","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T10:03:44Z","timestamp":1569578624000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Exercise during preoperative therapy increases tumor vascularity in pancreatic tumor patients"],"prefix":"10.1038","volume":"9","author":[{"given":"Claudia Alvarez","family":"Florez Bedoya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9612-2285","authenticated-orcid":false,"given":"Ana Carolina Ferreira","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4797-4147","authenticated-orcid":false,"given":"An","family":"Ngo-Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Q.","family":"Petzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fogelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador Gabriel","family":"Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huamin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjeong","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew H. G.","family":"Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri L.","family":"Schadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,27]]},"reference":[{"key":"49582_CR1","doi-asserted-by":"publisher","first-page":"E326","DOI":"10.1188\/14.ONF.E326-E342","volume":"41","author":"S Mishra","year":"2014","unstructured":"Mishra, S., Snyder, S. R., Geigle, C., Gotay, P. & Are, C. exercise programs effective for improving health-related quality of life among cancer survivors? A systematic review and meta-analysis. Oncology Nursing Forum 41, E326\u2013E342, https:\/\/doi.org\/10.1188\/14.ONF.E326-E342 (2014).","journal-title":"Oncology Nursing Forum"},{"issue":"11","key":"49582_CR2","doi-asserted-by":"publisher","first-page":"e26567","DOI":"10.1002\/pbc.26567","volume":"64","author":"Vanessa Rustler","year":"2017","unstructured":"Rustler, V. et al. Exercise interventions for patients with pediatric cancer during inpatient acute care: A systematic review of literature. Pediatric Blood & Cancer, e26567-n\/a, https:\/\/doi.org\/10.1002\/pbc.26567 (2017).","journal-title":"Pediatric Blood & Cancer"},{"key":"49582_CR3","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1200\/jco.2017.77.5809","volume":"36","author":"JM Scott","year":"2018","unstructured":"Scott, J. M. et al. Efficacy of Exercise Therapy on Cardiorespiratory Fitness in Patients With Cancer: A Systematic Review and Meta-Analysis. Journal of Clinical Oncology 36, 2297\u20132305, https:\/\/doi.org\/10.1200\/jco.2017.77.5809 (2018).","journal-title":"Journal of Clinical Oncology"},{"key":"49582_CR4","doi-asserted-by":"publisher","unstructured":"McCullough, D. J., Stabley, J. N., Siemann, D. W. & Behnke, B. J. Modulation of Blood Flow, Hypoxia, and Vascular Function in Orthotopic Prostate Tumors During Exercise. Journal of the National Cancer Institute 106, https:\/\/doi.org\/10.1093\/jnci\/dju036 (2014).","DOI":"10.1093\/jnci\/dju036"},{"key":"49582_CR5","doi-asserted-by":"publisher","unstructured":"Betof, A. S. et al. Modulation of Murine Breast Tumor Vascularity, Hypoxia, and Chemotherapeutic Response by Exercise. Journal of the National Cancer Institute 107, https:\/\/doi.org\/10.1093\/jnci\/djv040 (2015).","DOI":"10.1093\/jnci\/djv040"},{"key":"49582_CR6","doi-asserted-by":"publisher","first-page":"65429","DOI":"10.18632\/oncotarget.11748","volume":"7","author":"KL Schadler","year":"2016","unstructured":"Schadler, K. L. et al. Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy. Oncotarget 7, 65429\u201365440, https:\/\/doi.org\/10.18632\/oncotarget.11748 (2016).","journal-title":"Oncotarget"},{"key":"49582_CR7","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1007\/s00423-017-1599-0","volume":"402","author":"A Ngo-Huang","year":"2017","unstructured":"Ngo-Huang, A. et al. Home-based exercise during preoperative therapy for pancreatic cancer. 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