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        Polymorphisms in TYMS for Prediction of Capecitabine-Induced Hand-Foot Syndrome in Chinese Patients with Colorectal Cancer

        Si-Qi Dong,Tong-Min Wang,Jiang-Bo Zhang,Yong-Qiao He,Wen-Qiong Xue,Zi-Yi Wu,Da-Wei Yang,Lian-Jing Cao,Jing-Wen Huang,Xi-Zhao Li,Pei-Fen Zhang,Xiao-Hui Zheng,Wei-Hua Jia 대한암학회 2021 Cancer Research and Treatment Vol.53 No.3

        Purpose Capecitabine is an extensively used oral prodrug of 5-fluorouracil in treatment of colon cancer and is known to cause hand-foot syndrome (HFS). As the target enzyme for capecitabine, thymidylate synthase (TYMS) plays a key role for 5-fluorouracil metabolism and has been associated with some side effects caused by capecitabine. The aim of our study is to identify the possible genetic predictors of capecitabine-induced HFS (CAP-HFS) in Chinese colorectal cancer patients.Materials and Methods Whole exons of TYMS were sequenced for 288 extreme phenotype HFS patients, including 144 severe or early-onset (first 2 cycles) moderate HFS extreme cases and 144 extreme controls with no reported HFS. The associations between polymorphisms and CAP-HFS were analyzed using logistic regression under an additive model.Results We identified a novel risk mutation (c.1A>G, chr18:657743), was associated with severe HFS in an extreme case who was affected during the first cycle of treatment. Moreover, we identified three new variants, rs3786362, rs699517, rs2790, and two previously reported variants, 5’VNTR 2R/3R and 3′-untranslated region 6-bp ins-del, which were significantly associated with CAP-HFS (p < 0.05). In silico analysis revealed that the effect of these polymorphisms in the TYMS region on the development of HFS might not be restricted solely to the regulation of TYMS expression, but also the TYMS catalytic activity through the indirect effect on ENOSF1 expression.Conclusion This study identified new polymorphisms in TYMS gene significantly associated with CAP-HFS, which may serve as useful genetic predictors for CAP-HFS and help to elucidate the underlying mechanism of HFS.

      • Therapeutic Effects and Adverse Drug Reactions are Affected by Icotinib Exposure and CYP2C19 and EGFR Genotypes in Chinese Non-Small Cell Lung Cancer Patients

        Chen, Jia,Zheng, Xin,Liu, Dong-Yang,Zhao, Qian,Wu, Yi-Wen,Tan, Fen-Lai,Wang, Yin-Xiang,Jiang, Ji,Hu, Pei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

        Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

      • KCI등재후보

        Analysis of Volatile Compounds of Jasmine Scented Tea during the Orthodox Manufacturing Process Using HS-SPME/GC-MS

        Jian Lu,De-Jun Fu,Dong-Fen Wu,Yu Liu,Yao-Ping Luo 한국차학회 2015 한국차학회지 Vol.- No.S

        Volatile components of jasmine-scented tea during the orthodox manufacturing process were extracted using Headspace solid-phase microextraction (HS-SPME) and the major flavor compounds were identified by Gas chromatography-mass spectrometry/Retention indices (GC-MS/RI). The major volatile compounds extracted by SDE could also be obtained by HS-SPME, which appears more suitable for extraction of aromatic compounds, for its advantages of simplicity and convenience. The GC-MS chromatograms of tea samples showed that the aromatic constituents of jasmine tea had been identified in composition after 1st scenting, which contained 6 apparently high peaks representing linalool, benzyl acetate, α-farnesene, (Z)-3-hexenyl benzoate, methyl anthranilate, and indole. According to the change of peak area of major volatile compounds, (Z)-3-hexenyl acetate and (Z)-3-hexenyl butyrate with green grass aroma reduced by 71.13% and 63.10% respectively in jasmine tea product, while 7 compounds with favorable flowery fruity aroma-benzyl acetate, (Z)-3-hexenyl benzoate, linalool, benzyl alcohol, α-farnesene, methyl anthranilate and indole- increased by 17.84%, 28.33 times, 32.49%, 1.70 times, 6.67 times, 11.84 times and 21.48 times respectively, comparing to the base tea. Besides, nerolidol (fruity-flowery) and germacrene D (woody), not detected in the base tea also gradually increased. The quality grade of jasmine tea was potentially correlated to the ratio of peak area of the 9 favorable compounds to that of the 2 grass compounds. After 1st scenting, the peak areas of compounds from jasmine flower increased by 1.81×105-18.24×105, and decreased by 36.14%-69.95% after the 1st drying. The peak areas of some components detected in both the base tea and jasmine flowers, like (Z)-3-hexenyl acetate and methyl salicylate, increased by 9.05%-57.60% of those of the base tea after 1st scenting, and lost more than 100% after the 1st drying, while the increased peak areas of some other components both detected, like α-farnesene and indole, were more than peak areas of the base tea, with 30%- 95% loss after the 1st drying. The content change tendency of volatiles during 2nd scenting and the 2nd drying were consistent with those during 1st scenting and the 1st drying. After raising fragrance, the contents of some low boiling point volatiles and compounds not detected in the base tea increased.

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