Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer

被引:32
作者
Brown, Justin C. [1 ]
Rhim, Andrew D. [2 ]
Manning, Sara L. [3 ]
Brennan, Luke [3 ]
Mansour, Alexandra I. [3 ]
Rustgi, Anil K. [4 ]
Damjanov, Nevena [4 ]
Troxel, Andrea B. [5 ]
Rickels, Michael R. [4 ]
Ky, Bonnie [4 ]
Zemel, Babette S. [4 ,6 ]
Courneya, Kerry S. [7 ]
Schmitz, Kathryn H. [8 ]
机构
[1] Dana Farber Canc Inst, Boston, MA 02115 USA
[2] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
[3] Univ Michigan, Med Sch, Ann Arbor, MI 48109 USA
[4] Univ Penn, Philadelphia, PA 19104 USA
[5] NYU, New York, NY USA
[6] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
[7] Univ Alberta, Edmonton, AB, Canada
[8] Penn State Coll Med, Hershey, PA USA
基金
美国国家卫生研究院;
关键词
SURROGATE END-POINTS; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; INSULIN-RESISTANCE; GROWTH-FACTOR; SHEAR-STRESS; BLOOD-FLOW; MORTALITY; SURVIVORS; OBESITY;
D O I
10.1371/journal.pone.0204875
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Physical activity is associated with a lower risk of disease recurrence among colon cancer patients. Circulating tumor cells (CTC) are prognostic of disease recurrence among stage I-III colon cancer patients. The pathways through which physical activity may alter disease outcomes are unknown, but may be mediated by changes in CTCs. Methods Participants included 23 stage I-III colon cancer patients randomized into one of three groups: usual-care control, 150 min-wk-1 of aerobic exercise (low-dose), and 300 min-wk-1 of aerobic exercise (high-dose) for six months. CTCs from venous blood were quantified in a blinded fashion using an established microfluidic antibody-mediated capture device. Poisson regression models estimated the logarithmic counts of CTCs. Results At baseline, 78% (18/23) of patients had >= 1 CTC. At baseline, older age (-0.12+/- 0.06; P=0.04), lymphovascular invasion (0.63+/-0.25; P=0.012), moderate/poor histology (1.09 +/-0.34; P=0.001), body mass index (0.07+/-0.02; P=0.001), visceral adipose tissue (0.08 +/-0.04; P=0.036), insulin (0.06+/-0.02; P=0.011), sICAM-1 (0.04+/-0.02; P=0.037), and sVCAM-1 (0.06+/-0.03; P=0.045) were associated with CTCs. Over six months, significant decreases in CTCs were observed in the low-dose (-1.34+/-0.34; P<0.001) and high-dose (-1.18+/-0.40; P=0.004) exercise groups, whereas no significant change was observed in the control group (-0.59+/-0.56; P=0.292). Over six months, reductions in body mass index (-0.07+/-0.02; P=0.007), insulin (-0.08+/-0.03; P=0.014), and sICAM-1 (-0.07+/-0.03; P=0.005) were associated with reductions in CTCs. The main limitations of this proof-of-concept study are the small sample size, heterogenous population, and per-protocol statistical analysis. Conclusion Exercise may reduce CTCs among stage I-III colon cancer patients. Changes in host factors correlated with changes in CTCs. Exercise may have a direct effect on CTCs and indirect effects through alterations in host factors. This hypothesis-generating observation derived from a small pilot study warrants further investigation and replication.
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页数:13
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