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Real-time Quantitative Study for Rhythmic Profiles of Dihydr...

Real-time Quantitative Study for Rhythmic Profiles of Dihydropyrimidine Dehydrogenase,and Thymidylate Synthase in mRNA Level on Nasopharyngeal Carcinoma Patients

作     者:LEVI Francis 

会议名称:《2006全国时间生物医学学术会议》

会议日期:2006年

学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

关 键 词:Chrono-chemotherapy Nasopharyngeal Carcinoma Dihydropyrimidine dehydrogenase Thymidylate synthase 

摘      要:In Southern China,chrono-chemotherapy has been tried to treat nasopharyngeal carcinoma (NPC) patients using 5-Fu combined with platinum complexes. However,there was no enough data about circadian profiles of the circadian profiles of dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS) in mRNA level on Chinese NPC patients. In present study,total of 13 NPC patients were involved,9 males and 4 *** veinal blood was collected at 6 time points (12:00,16:00,20:00,and 24:00,04:00,08:00) during a single 24 hours from all the participants. The circadian gene expression profiles of DPD,TS in PBMC were measured using the real-time quantitative RT-PCR method. In addition, the whole-blood reduced Glutathione (GSH), Dihydrouracil and uracil ratios (UH2/U ratios)(an indirect method for measuring DPD activity, HPLC method), plasma cortisol level were also measured. In present study, Mesor (rhythm-adjust mean) of DPD gene copies was 6.21×107±7.76±106 copy/μg RNA (mesor±SEM), and it was 828×103±8.33×102 copy/ug RNA for TS gene. It was of no statistical significance for DPD mRNA expression according to sampling time (ANOVA for Repeated Measures,F= 1.067,P=0.369;Cosinor,P=0.078), and for TS (ANOVA for Repeated Measures, F= 0.505, P = 0.765, Cosinor, P = 0.1068). The plasma cortisol displayed a clearly circadian rhythm and the peak time located at 09:14±01:11 (Corsinor, P 0.0001). The mean value of UH2/U was 4.80±0.20 and a significant circadian rhythm was not displayed (ANOVA for Repeated Measures, F= 0.352,P = 0.862;Corsinor, P = 03053). The mesor value of GSH was 19.60±1.11 (nmol/L) and GSH displayed a possible circadian rhythm and the acrophase located at 05:02 (ANOVA for Repeated Measures,F= 3.985, P = 0.050;Corsinor, P=0.0645). In conclusion, a clear circadian rhythm was not displayed for DPD gene and TS gene in mRNA level, also not found for DPD activity on Chinese NPC patients, although these patients still maintained an obvious circadian rhythm in

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