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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.
Enhanced drought and salinity tolerance in transgenic potato plants with a BADH gene from spinach
Zhang, Ning,Si, Huai-Jun,Wen, Gang,Du, Hong-Hui,Liu, Bai-Lin,Wang, Di The Korean Society of Plant Biotechnology 2011 Plant biotechnology reports Vol.5 No.1
Drought and salinity are the most important abiotic stresses that affect the normal growth and development of plants. Glycine betaine is one of the most important osmolytes present in higher plants that enable them to cope with environmental stresses through osmotic adjustment. In this study, a betaine aldehyde dehydrogenase (BADH) gene from spinach under the control of the stress-induced promoter rd29A from Arabidopsis thaliana was introduced into potato cultivar Gannongshu 2 by the Agrobacterium tumefaciens system. Putative transgenic plants were confirmed by Southern blot analysis. Northern hybridization analysis demonstrated that expression of BADH gene was induced by drought and NaCl stress in the transgenic potato plants. The BADH activity in the transgenic potato plants was between 10.8 and 11.7 U. There was a negative relationship (y = -2.2083x + 43.329, r = 0.9495) between BADH activity and the relative electrical conductivity of the transgenic potato plant leaves. Plant height increased by 0.4-0.9 cm and fresh weight per plant increased by 17-29% for the transgenic potato plants under NaCl and polyethylene glycol stresses compared with the control potato plants. These results indicated that the ability of transgenic plants to tolerate drought and salt was increased when their BADH activity was increased.
Si-Qi Tang,Ling-Long Tang,Yan-Ping Mao,Wen-Fei Li,Lei Chen,Yuan Zhang,Ying Guo,Qing Liu,Ying Sun,Cheng Xu,Jun Ma 대한암학회 2021 Cancer Research and Treatment Vol.53 No.2
Purpose The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. Materials and Methods Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software.Results Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031).Conclusion This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.
Zhang Yan-Ze,Chen Xiao-Yue,Si Jun-Jie,He Ze-Yu,Wen Xi-Shan 대한전기학회 2023 Journal of Electrical Engineering & Technology Vol.18 No.5
Disconnector operation in GIS generates VFTO and TEV, which threaten device insulation and personnel safety. In order to calculate VFTO and TEV more accurately, this paper proposes a VFTO-TEV joint simulation model. Among them, dynamic arc model is used to reflect the dynamic characteristics of high frequency AC arc. In order to reflect the electromagnetic leakage phenomenon caused by the impedance mismatch of high-frequency electromagnetic waves, and the influence of the transient potential difference formed by the transient electromagnetic field on grounding grid on TEV, the geometric structures of high-voltage bushing, grounding pillars and grounding grid are modeled to obtain their respective frequency-dependent admittance matrices, which are converted into corresponding broadband equivalent circuit models by combining vector fitting method and impedance synthesis method. The above modeling method is applied to the 1000 kV GIS test circuit, and the simulation model is built in the ATP-EMTP electromagnetic transient program, and the joint simulation research of VFTO and TEV is carried out. The results show that at each measurement point of the test circuit, the amplitude error of the VFTO obtained by simulation and actual measurement is mostly less than 7%, and the frequency spectrum both contains the main frequency components of 18 MHz and 25 MHz; Compared with the traditional calculation model of obtaining VFTO/TEV using CIGRE model/Petersen's law, the amplitude of VFTO and TEV obtained by joint simulation model is lower and contains richer high-frequency components. In addition, the opening speed of 0.8 m/s also corresponds to the maximum point of the VFTO amplitude of the test circuit. Finally, based on the above modeling method, the effectiveness of adding ferrite beads to suppress VFTO is verified by simulation. © 2017 Elsevier Inc. All rights reserved.
Wang, Wen-Jia,Qin, Si-Hao,Zhang, Ji-Wei,Jiang, Yue-Yao,Zhang, Jin-Nan,Zhao, Lei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22
Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.
Fu, Si-Rui,Zhang, Ying-Qiang,Li, Yong,Hu, Bao-Shan,He, Xu,Huang, Jian-Wen,Zhan, Mei-Xiao,Lu, Li-Gong,Li, Jia-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7
Background: Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however, treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the cost of treatment. The consequences of sorafenib discontinuation and continuation are uncertain. Materials and Methods: We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013. Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP) were compared for survival analysis. Cox proportional hazard regression was performed to assess the effect of important factors on OS in the overall patient population and on pOS in patients who continued sorafenib treatment. Results: Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The median OS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) were statistically different between the discontinuation and continuation groups. Neither the median time to first PD nor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the 24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correction for confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS in patients who continued sorafenib treatment. Conclusions: Sorafenib discontinuation may cause HCC flares or outbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with Barcelona Clinic Liver Cancer stage B disease or only intrahepatic PD.
Optimization of Nominal Mixing Ratio of Mg to B in Fabrication of Magnesium Diboride Bulk
Yun Zhang,Cheng Lu,Si Hai Zhou,Kookchae Chung,Wen Xian Li IEEE 2009 IEEE transactions on applied superconductivity Vol.19 No.3
<P>In this paper bulk magnesium diboride (Mg<SUB>x</SUB>B<SUB>2</SUB>) with x varying from 0.9 to 1.3 was prepared by solid state reaction. The Mg:B mixing ratio for ideal MgB<SUB>2</SUB> is 1:2. The samples were sintered at 800degC for 60 h. Quantitative X-ray diffraction (XRD) analysis was performed to obtain the lattice parameters, the microstrain, and the weight fraction of impurities using the Rietveld refinement method. It has been found that the fraction of pure MgB<SUB>2</SUB> phase increases from x = 0.9 to x = 1.1, and then decreases with further increases in x. Mg<SUB>1.1</SUB>B<SUB>2</SUB> exhibits the highest critical current density, J<SUB>c</SUB>, over other samples in both low fields and high fields. A direct correlation between J<SUB>c</SUB> and connectivity indicates that better connectivity, caused by smaller amounts of impurities, results in the best J<SUB>c</SUB> in Mg<SUB>1.1</SUB>B<SUB>2</SUB>.</P>