ABSTRACT
Predicting patient responses to chemotherapy regimens is a major challenge in cancer treatment. Experimental model systems coupled with quantitative mathematical models to calculate optimal dose and frequency of drugs can enable improved chemotherapy regimens. Here we developed a simple approach to track two-dimensional cell colonies composed of chemo-sensitive and resistant cell populations via fluorescence microscopy and coupled this to computational model predictions. Specifically, we first developed multiple 4T1 breast cancer cell lines resistant to varying concentrations of doxorubicin, and demonstrated how heterogeneous populations expand in a two-dimensional colony. We subjected cell populations to varied dose and frequency of chemotherapy and measured colony growth. We then built a mathematical model to describe the dynamics of both chemosensitive and chemoresistant populations, where we determined which number of doses can produce the smallest tumor size based on parameters in the system. Finally, using an in vitro model we demonstrated multiple doses can decrease overall colony growth as compared to a single dose at the same total dose. In the future, this system can be adapted to optimize dosing strategies in the setting of heterogeneous cell types or patient derived cells with varied chemoresistance.
ABSTRACT
UNLABELLED: Clinicians surmise that the application of external ankle support reduces the ability to perform functional skills and movements, but the outcomes from some of these studies have been inconclusive. PURPOSE: To meta-analyze studies regarding the effects of external ankle support on lower-extremity functional performance measures. METHODS: A total of 93 effects from 17 randomized controlled trials utilizing predominantly crossover designs with recreationally active participants and competitive athletes were subjected to a random-effects meta-analysis. The treatment variable was external ankle support with three levels: adhesive tape, lace-up style, and semirigid style. Differences between mean changes in treatment and control groups were computed as standardized effect sizes for sprint, agility, and vertical jump performance with their 90% confidence intervals (CI). Effect sizes >0.20 were considered substantial. RESULTS: The greatest effect of ankle support on performance was a negative effect of lace-up style brace on sprint speed (effect size -0.22, 90% CI -0.47 to 0.03), equivalent to approximately 1% impairment of speed. The other effects of external ankle support on performance were insubstantial, though most were negative, and their lower confidence limits allowed for realistic chances of impaired performance. Substantial true variation between studies, although poorly defined, was also present for some effects, further increasing the likelihood of performance impairment in some settings. CONCLUSIONS: More research is needed to reduce the uncertainty in the effects of external ankle support on performance. In the meantime, it is our opinion that the benefit in preventing injury outweighs the possibility of substantial but small impairment of performance when athletes use external ankle support.
