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Daily locomotor activity declines with tumor growth and disease progression in glioblastoma
Maria F. Gonzalez-Aponte, Sofia V. Salvatore, Anna R. Damato, Ruth G.N. Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog
Maria F. Gonzalez-Aponte, Sofia V. Salvatore, Anna R. Damato, Ruth G.N. Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog
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Research Article Clinical Research Neuroscience Oncology

Daily locomotor activity declines with tumor growth and disease progression in glioblastoma

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Abstract

Glioblastoma (GBM) is an aggressive brain tumor that often progresses despite resection and treatment. Timely and continuous assessment of GBM progression is critical to expedite secondary surgery or enrollment in clinical trials. However, current progression detection requires costly and specialized MRI examinations, which, in the absence of new symptoms or signs, are usually scheduled every 2–3 months. Here, we hypothesized that changes in daily activity are associated with GBM growth and disease progression. We found that wheel-running activity in GBM-bearing mice declined as tumors grew and preceded weight loss and circadian breakdown by over a week. Temozolomide treatment in the morning, but not evening, significantly reduced tumor size and restored daily locomotion in mice. In a pilot study of 6 patients with GBM wearing an actigraphy watch, wrist movement provided a feasible and continuous longitudinal indicator of daily activity with 1-minute resolution. After tumor resection and radiation, daily activity declined in 2 patients 19 and 55 days before detection of progression by MRI but did not change for the 4 patients with stable disease. These results suggest that daily activity tracking using wearable devices may serve as a real-time indicator and potential monitoring tool for GBM progression and treatment efficacy.

Authors

Maria F. Gonzalez-Aponte, Sofia V. Salvatore, Anna R. Damato, Ruth G.N. Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog

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Figure 3

Delivering TMZ in the morning reduced GBM tumor size and restored baseline daily locomotor activity.

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Delivering TMZ in the morning reduced GBM tumor size and restored baseli...
(A and B) GL261 xenografts decreased in size when treated with morning (A) or evening TMZ (B) com¬pared with vehicle (AM: **P < 0.01 from days 20 to 26; PM: *P < 0.05 from days 22 to 26; mean ± SEM, 2-way ANOVA with Tukey’s multiple-comparison test). Arrows indicate days of TMZ or vehicle treatment. (C and D) Mice receiving morning (C) or evening (D) TMZ recovered locomotion compared to vehicle (*P < 0.05; **P < 0.01; Mean ± SEM, 2-way ANOVA with Tukey’s multiple-comparison test). (E and F) Daily locomotion did not correlate with tumor size in mice receiving morning TMZ (r = –0.34, 95% CI: –0.69 to 0.11, P = 0.12) but negatively correlated with tumor size in mice receiving evening TMZ (r = –0.94, 95% CI: –0.98 to –0.87, P < 0.0001). Each dot represents daily average of each mouse, excluding days of surgery and recovery. (G) Daily locomotion negatively correlated with tumor size in vehicle-treated mice (r = –0.95, 95% CI: –0.98 to –0.87, P < 0.0001). (H) Body weight declined 18 days after implant in mice treated with vehicle or evening TMZ and increased in mice treated with morning TMZ (mean ± SEM, 2-way ANOVA with Tukey’s multiple-comparison test, *P < 0.05 TMZ am vs. TMZ pm, and TMZ am vs. vehicle).

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