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Ke Yang,Yifan Chen,Kenneth Kin Wah To,Fang Wang,Delan Li,Likun Chen,Liwu Fu 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo. Mechanistically, alectinib increased the intracellular accumulation of ABCB1/ABCG2 substrates such as doxorubicin (DOX) and Rhodamine 123 (Rho 123) by inhibiting the efflux function of the transporters in ABCB1- or ABCG2-overexpressing cells but not in their parental sensitive cells. Furthermore, alectinib stimulated ATPase activity and competed with substrates of ABCB1 or ABCG2 and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling bound to ABCB1 or ABCG2 but neither altered the expression and localization of ABCB1 or ABCG2 nor the phosphorylation levels of AKT and ERK. Alectinib also enhanced the cytotoxicity of DOX and the intracellular accumulation of Rho 123 in ABCB1-overexpressing primary leukemia cells. These findings suggest that alectinib combined with traditional chemotherapy may be beneficial to patients with ABCB1- or ABCG2-mediated MDR.
Fault Detection for a Class of Closed-loop Hypersonic Vehicle System via Hypothesis Test Method
Xunhong Lv,Yifan Fang,Zehui Mao,Bin Jiang,Ruiyun Qi 제어·로봇·시스템학회 2021 International Journal of Control, Automation, and Vol.19 No.1
This paper studies the fault detection problem for a class of hypersonic vehicle with actuator faults,disturbances and random noises. To handle the unknown disturbances, an unknown input Kalman filter (UIKF) ispresented to estimate the unknown system states and disturbances, simultaneously. Considering that the closed-loopstructure brings the robustness to the hypersonic vehicle, which could cover some faults, the Total Measurable FaultInformation Residual (ToMFIR) is employed as the fault detection residual. Moreover, to deal with the randomnoises, the hypothesis testing method is utilized to obtain the thresholds under some fault detection performances(false alarm rate and missing alarm rate). The fault detectability condition is also derived. Finally, the simulationsverify the effectiveness of the proposed fault detection method