Involvement of riboflavin kinase expression in cellular sensitivity against cisplatin
INTERNATIONAL JOURNAL OF ONCOLOGY
Authors: Hirano, Gen; Izumi, Hiroto; Yasuniwa, Yoshihiro; Shimajiri, Shohei; Wang Ke-Yong; Sasagiri, Yasuyuki; Kusaba, Hitoshi; Matsumoto, Kaori; Hasegawa, Tetsuya; Akimoto, Masayuki; Akashi, Koichi; Kohno, Kimitoshi
Abstract
Flavin adenine dinucleotide (FAD) is an essential coenzyme for glutathione reductase (GR) which catalyzes the reduction of oxidized glutathione to regenerate the reduced form involved in protection against oxidative stress. Riboflavin kinase (RFK) also known as flavokinase is involved in the first step of bioactivation of riboflavin (RF) to form flavin mononucleotide (FMN) which can be subsequently converted to FAD in an ATP-dependent reaction catalyzed by FAD synthetase (FADS). We investigated the involvement of RFK in cisplatin resistance using human prostate cancer PC3 cells. RFK overexpression renders cells resistant not only to cisplatin but also to hydrogen peroxide (H2O2) and diamide. Furthermore, knockdown of RFK expression induced apoptosis. We demonstrated that overexpression of RFK increased the levels of FAD, FMN and total glutathione and the expression of GR and glutathione S-transferase-n (GSTa). RFK expression is up-regulated in cisplatin-resistant P/CDP6 cells in addition to FAD, total glutathione level, GR and GSM. Knockdown of RFK expression also sensitized both PC3 and P/CDP6 cells to cisplatin. Moreover, cellular levels of RFK expression correlate well with Gleason score, known as a good indicator of patient prognosis. The present study suggests that RFK expression is involved not only in cellular protection from oxidative stress but also in malignant progression of prostate cancer.
Assessment of ionospheric corrections for PPP-RTK using regional ionosphere modelling
MEASUREMENT SCIENCE AND TECHNOLOGY
Authors: Psychas, D.; Verhagen, S.; Liu, X.; Memarzadeh, Y.; Visser, H.
Abstract
This paper presents an analysis of the ionospheric corrections required to get a significant improvement in PPP-RTK performance. The main aim was to determine the improvement in the position precision and time-to-first-fix in the PPP-RFK user side using ionospheric corrections computed from a network. The study consists of two main steps. The first one includes an empirical investigation of the ionosphere model precision necessary to greatly improve the PPP-RTK performance in a simulated environment in terms of precision and convergence time. In the second one, an optimal ionosphere representation was developed to provide precise ionospheric corrections by parameterizing the ionospheric slant delays after the PPP-RTK network processing in terms of ionosphere model coefficients and differential code biases using real GNSS measurements. Experimental results demonstrate that the proposed methodology can be used for reliable regional ionosphere modeling and satellite code bias estimation, due to the consistency of the satellite code bias estimates with those provided from the International GNSS Service Analysis Centres, the high stability of the estimated receiver and satellite code biases and the low least-squares residuals of the network-based ionosphere modeling solution. Finally, it has been shown that the precision of ionospheric corrections at zenith needs to be better than 5 cm to enable faster PPP-RTK solutions.