Although anti-cancer treatments have significantly advanced over the past decades, obstacles to accomplishing successful treatment still exist. The occurrence of treatment resistance is one of the... Show moreAlthough anti-cancer treatments have significantly advanced over the past decades, obstacles to accomplishing successful treatment still exist. The occurrence of treatment resistance is one of the major factors that limit the long-lasting efficacy of anti-cancer treatment. Additionally, substantial variability in pharmacokinetics (PK) / pharmacodynamics (PD) of anti-cancer drugs also challenges successful oncology treatment. Therefore, gaining knowledge of and ultimately better suppressing evolutionary resistance development during treatment, and applying personalized treatment are desired to improve anti-cancer treatment. In this thesis, we have applied quantitative modeling approaches to address these needs, aiming for improved treatment for oncology patients. Our work demonstrated that with the quantitative models, the evolutionary progression of tumors could be characterized and predicted, accounting for interactions among heterogeneous tumor cells and supported by mutant gene variants detected in circulating tumor DNA (ctDNA). In addition, we developed population PK /PD models which enabled quantitative description of the PK and PD of anti-cancer drugs and corresponding variabilities in real-world patients. The developed models have been further applied to support the identification of optimal treatment strategies and guide individualized treatment for oncology patients. Show less
In mammals, an endogenous clock located in the suprachiasmatic nucleus (SCN), synchronizes physiological and biological rhythms to the environmental light–dark cycle. In experiments, most... Show moreIn mammals, an endogenous clock located in the suprachiasmatic nucleus (SCN), synchronizes physiological and biological rhythms to the environmental light–dark cycle. In experiments, most researchers applied rectangular scheme as the external light–dark scheme received by the SCN neuronal oscillators. However, the external light intensity changes gradually throughout the day. Therefore, trapezoidal schemes (twilight) or sinusoidal schemes were also applied. Thus far, the effects of different light–dark schemes on the oscillators of the SCN did not get fully explored. In the present study, we theoretically analyzed how the five common light–dark schemes affect the entrainment ability of the SCN, based on a Poincaré model. We numerically found that when the maximum light intensity, the minimum light intensity, and the total amount of light exposure per cycle were the same, the largest entrainment range was obtained in the oscillators receiving more light in the daytime. However if, under the condition of 12:12-h illumination, the total amount of light exposure per cycle was the same, the maximum light intensity during the day leaded to an increased range of entrainment. Moreover, the entrainment range was reduced when the photoperiod was extended. Note that, increasing the maximum light intensity increased the entrainment ability of all light–dark schemes. Our results exposes the important role of light–dark schemes in the entrainment ability of the SCN network, and provides a potential explanation for the diversity of the entrainment range between diurnal and nocturnal animals. Show less
