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Genetic Evidence for xpc-KRAS Interactions During Lung Cancer Development

Journal of Genetics and Genomics 2015年第10期42卷 589-596页

作者： Xiaoli Zhang Nonggao He Dongsheng Gu Jeff Wickliffe James Salazar Istavan Boldogh Jingwu Xie Department of Pediatrics Wells Center for Pediatrics Research Indiana University School of Medicine University of Texas Medical Branch School of Medicine Cancer Center Department of Global Environmental Health Sciences Tulane University School of Public Health Biology Department Galveston College Department of Microbiology and Immunology University of Texas Medical Branch School of Medicine

Lung cancer causes more deaths than breast, colorectal and prostate cancers combined. Despite major advances in targeted therapy in a subset of lung adenocarcinomas, the overall 5-year survival rate for lung cancer worldwide has not significantly changed for the last few decades. DNA repair deficiency is known to contribute to lung cancer development. In fact, human polymorphisms in DNA repair genes such as xeroderma pigmentosum group C （xpc） are highly associated with lung cancer incidence. However, the direct genetic evidence for the role of xpc for lung cancer development is still lacking. Mutations of the Kirsten rat sarcoma viral oncogene homolog （Kras） or its downstream effector genes occur in almost all lung cancer cells, and there are a number of mouse models for lung cancer with these mutations. Using activated Kras, KrasTM, as a driver for lung cancer development in mice, we showed for the first time that mice with KrasTM and xpc knockout had worst outcomes in lung cancer development, and this phenotype was associated with accumulated DNA damage. Using cultured ceils, we demonstrated that induced expression of oncogenic KR.ASG12v led to increased levels of reactive oxygen species （ROS） as well as DNA damage, and both can be suppressed by anti-oxidants. Our results suggest that xpc may help repair DNA damage caused by KRAS-mediated production of ROS.

关键词： Lung cancer xpc Kras ROS

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xpc Polymorphism Increases Risk of Digestive System Cancers:Current Evidence from A Meta-Analysis

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Chinese Journal of Cancer Research 2012年第3期24卷 181-189页

作者： Xia Jiang Li-tao Zhou Shan-chun Zhang Kun Chen Department of Epidemiology and Health Statistics Zhejiang University School of MedicineHangzhou 310058China

Objective： Xeroderma pigmentosum complementation group C （xpc） participates in the initial recognition of DNA damage during nucleotide excision repair process in global genomic repair. Our meta-analysis was performed to evaluate the association between three polymorphisms （Lys939Gln, PAT＋/- and Ala499Val） of xpc gene and risk of digestive system cancers. Methods： All the relevant case-control studies published to April 2011 were identified through searching PubMed. Digestive system cancer risk with the three polymorphisms was estimated for each study by odds ratio （OR） with its 95% confidence interval （95% CI）. Results： We found an increased overall risk for digestive system cancers in all three models of Lys939Gln AC （AC/CC vs. AA： OR, 1.20; 95% CI, 1.11-1.30; CC vs. AC/AA： OR, 1.24; 95% CI, 1.11-1.39; CC vs. AA： OR, 1.36; 95% CI, 1.21-1.53）. When strati？ed by ethnicity, results remained significant in Asian population （AC/CC vs. AA： OR, 1.18; 95% CI, 1.02-1.37; CC vs. AC/AA： OR, 1.32; 95% CI, 1.1-1.51; CC vs. AA： OR, 1.35; 95% CI, 1.08-1.70）, but not for Caucasians. However for Ala499Val CT, a significant protective effect of T allele was only observed in the dominant model. Otherwise, no significant results were observed for PAT＋/-. Conclusion： xpc Lys939Gln AC polymorphism may play an important role in digestive system cancer susceptibility.

关键词： xpc Polymorphism Digestive system cancer Meta-anaiysis

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The involvement of xpc protein in the cisplatin DNA damaging treatment-mediated cellular response

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Cell Research 2004年第4期14卷 303-314页

作者： Alan DOMBKOWSKI Lynn CHUANG Institute of Environmental Health Sciences Wayne State University 2727 Second Avenue Detroit MI 48201 USA

Recognition of DNA damage is a critical step for DNA damage-mediated cellular response. xpc is an important DNA damage recognition protein involved in nucleotide excision repair (NER). We have studied the xpc protein in cisplatin DNA damaging treatment-mediated cellular response. Comparison of the microarray data from both normal and xpc-defective human fibroblasts identified 861 xpc-responsive genes in the cisplatin treatment (with minimum fold change≥1.5). The cell cycle and cell proliferation-related genes are the most affected genes by the xpc defect in the treatment. Many other cellular function genes, especially the DNA repair and signal transduction-related genes, were also affected by the xpc defect in the treatment. To validate the microarray data, the transcription levels of some microarray-identified genes were also determined by an RT-PCR based real time PCR assay. The real time PCR results are consistent with the microarray data for most of the tested genes, indicating the reliability of th

关键词： xpc cisplatin DNA-damaging treatment microarray analysis.

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Matlab Based Human & Hardware-in-Loop Simulation for the Study on Vehicle Stability Control

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Journal of Shanghai Jiaotong university(Science) 2006年第4期11卷 498-505页

作者：张勇殷承良张建武 Inst. of Automotive Eng. Shanghai Jiaotong Univ.

This paper described an effective method to implement human & hardware in the loop simulation(HHILS), which is based on MATLAB system and can be used to study human driving actions in the abrupt situation and vehicle stability control(VSC). A hybrid control algorithm, which makes full use of the advantages of robust control and fuzzy logic, was adopted in VSC system. The results of HHILS show that HHILS’ application on the vehicle handling and VSC resarch is feasible. These results also confirm that the handling performance of the vehicle with VSC is improved obviously compared to the vehicle without VSC.

关键词： human & hardware-in-loop simulation vehicle stability control robust-fuzzy control Matlab xpc target virtual reality

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Pathways towards Precision Medicine in Cancer Management Using Genomic Information

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Journal of Genetics and Genomics 2015年第10期42卷 515-515,516页

作者： Jingwu Xie Department of Pediatrics Wells Center for Pediatrics Research Indiana University School of Medicine

Cancer research over the last few decades indicates that cancer is a genetic disease. In fact, the discovery of the most advanced targeted therapy of cancer comes from cancer ge- netics/genomics studies. This year marks the 20th anniversary for the invention of imatinib mesylate, which targets primarily the BCR-ABL kinase in Philadelphia chromosome-positive chronic myelogenous leukemia （CML）. Philadelphia chro- mosome is the most significant chromosomal aberration in leukemia, and imayinib mesylate is regarded as the first small molecule targeting mutant kinases in cancer. In the last few years, additional therapeutic drugs have been developed to target mutant EGFR and ALK fusion proteins in lung adeno- carcinomas. Thus, understanding the genomic aberrations has huge impacts on clinical management of cancer.

关键词： In gene EGFR xpc lung

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A real-time data smoothness method based on xpc-Target

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High Technology Letters 2010年第1期16卷 99-102页

作者：王熠 He Hongwen Lin Yi School of Mechanical Beijing Institute of Technology Beijing 100081 P.R. China Beijing Automobile Technology Center Beijing 100021 P.R. China

A method of real-time data smoothness which is applied in a hardware-in-the-loop (HIL) simulation platform for a plug-in hybrid electric vehicle synthetical power device is described. The input signal of the platform comes from a AC/DC switch power with output containing noises. A linear slide average arithmetic is applied to smooth the noises. To average a certain number input sample signals, this method can decrease the noises voltage level, which meet the requirement of the simulation platform. The efficiency and signal delay time are presented to describe the result of this method, and a statistical index is used to judge the arithmetic's efficiency. The tests results show that the arithmetic fit the requirement of the HIL simulation platform. © by High Technology Letters Press.

关键词：实时数据平滑方法 xpc 混合动力电动汽车算术平均数仿真平台基础输入信号

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基于xpc的驾驶员辅助系统硬件在环仿真试验台

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中国机械工程 2007年第16期18卷 2012-2015页

作者：李升波王建强李克强清华大学汽车安全与节能国家重点实验室北京100084

研发了基于xpc技术的驾驶员辅助系统硬件在环仿真试验台,以解决目前此类试验台开发成本高、难度大的问题。在基于xpc的总体方案基础上,建立了模块化的仿真模型,采用S函数驱动GUI界面的方法,解决了对硬件在环仿真过程进行实时监控的问题... 详细信息

研发了基于xpc技术的驾驶员辅助系统硬件在环仿真试验台,以解决目前此类试验台开发成本高、难度大的问题。在基于xpc的总体方案基础上,建立了模块化的仿真模型,采用S函数驱动GUI界面的方法,解决了对硬件在环仿真过程进行实时监控的问题。使用表明,该试验台具备较好的驾驶员在环仿真功能,能够对驾驶员辅助系统的软硬件进行验证与评价。

关键词：主动安全硬件在环驾驶员辅助 xpc

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xpc基因Ala499Val、Lys939Gln多态与食管癌、贲门癌发病风险的关联

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癌症 2006年第9期25卷 1113-1119页

作者：周荣秒李琰王娜张晓娟董秀娟郭炜河北省肿瘤研究所分子生物学研究室河北石家庄050011

背景与目的:xpc基因参与核苷酸切除修复,该基因存在单核苷酸多态性(SNP)位点,并可能通过SNP位点碱基的改变影响其修复能力及疾病易感性。本研究旨在探讨xpc基因第8外显子Ala499Val及第15外显子Lys939GlnSNP与河北省食管癌、贲门癌高发... 详细信息

背景与目的:xpc基因参与核苷酸切除修复,该基因存在单核苷酸多态性(SNP)位点,并可能通过SNP位点碱基的改变影响其修复能力及疾病易感性。本研究旨在探讨xpc基因第8外显子Ala499Val及第15外显子Lys939GlnSNP与河北省食管癌、贲门癌高发区—磁县和涉县人群食管鳞状细胞癌(esophagealsguamouscellcarcinoma,ESCC)和贲门腺癌(gastriccardiacadenocorcinoma,GCA)遗传易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法检测327例ESCC患者、253例GCA患者和612名健康对照的xpc基因第8外显子Ala499Val及第15外显子Lys939GlnSNP的基因型。结果:ESCC患者组、GCA患者组上消化道肿瘤家族史阳性个体比例明显高于对照组,上消化道肿瘤家族史可增加ESCC、GCA的发病风险(经性别和年龄校正后的OR=1.76和1.77,95%CI=1.34～2.32和1.31～2.39)。ESCC患者组和对照组的xpc基因第8外显子C、T等位基因频率及C/C、C/T、T/T基因型分布差异均无显著性(P>0.05)。GCA患者组T等位基因频率(26.5%)显著低于对照组(32.5%),两组相比差异有显著性(χ2=6.12,P=0.01);与C/C基因型相比,携带C/T基因型可显著降低GCA的发病风险(OR=0.62,95%CI=0.45～0.84)。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与C/C基因型相比,携带C/T基因型可显著降低吸烟个体和家族史阴性个体GCA的发病风险(OR均等于0.57,95%CI=0.36～0.91和0.37～0.88)。在ESCC、GCA患者组和对照组之间,xpc第15外显子A、C等位基因频率及A/A、A/C、C/C基因型分布差异均无显著性(P>0.05)。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与A/A基因型相比,携带C/C基因型可显著增加非吸烟个体ESCC的发病风险(OR=2.05,95%CI=1.15～3.66)。单体型分析显示,A/T、A/C、C/T、C/C四种单体型,在ESCC患者组与对照组之间分布差异无显著性(P>0.05);在GCA患者组与对照组之间分布差异有显著性(P=0.02)。与A/T单体型相比,携带A/C、C/C单体型可显著增加GCA的发病风险(OR=1.35和1.46,95%CI=1.01～1.81和1.06～2.00)。结论:在河北省食管癌、贲门癌高发区—磁县和涉县人群中,携带xpc基因第8外显子C/T基因型可能明显降低GCA的发病风险;第15外显子Lys939GlnSNP可能与ESCC、GCA的发病风险无关,但分层分析发现携带第15外显子C/C基因型可能增加非吸烟个体ESCC的发病风险;携带A/C、C/C单体型可能增加GCA的发病风险。

关键词：食管肿瘤鳞状细胞癌贲门肿瘤腺细胞癌 xpc 基因多态性肿瘤易感性中国河北

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基于xpc的地铁TCU实时仿真测试系统设计

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系统仿真学报 2007年第4期19卷 765-767,775页

作者：吴浩张峰李小波上海交通大学电气工程系上海200240 山东科技大学机电学院测控系山东266510

在讨论地铁牵引系统动态特性和控制原理的基础上,应用MATLAB的xpc Target工具箱,构建了针对牵引控制单元(TCU)的实时仿真测试平台。测试平台采用了基于网络的主副机结构,在实验室环境再现了机车正常运行的各种工况。还讨论了实现测试系... 详细信息

在讨论地铁牵引系统动态特性和控制原理的基础上,应用MATLAB的xpc Target工具箱,构建了针对牵引控制单元(TCU)的实时仿真测试平台。测试平台采用了基于网络的主副机结构,在实验室环境再现了机车正常运行的各种工况。还讨论了实现测试系统所需要的硬件、软件、和通信方式。对比分析了在线实时数据和实验室测试数据,证明了这种方法的有效性。

关键词：牵引控制单元斩波器半实物仿真 xpc 实时

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某型大柔性多体结构卫星半实物仿真

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系统仿真学报 2006年第5期18卷 1204-1207,1259页

作者：原劲鹏杨涤翟坤张子龙哈尔滨工业大学航天工程系黑龙江哈尔滨150001 上海航天控制工程研究所上海200233

介绍了xpc实时目标环境,借助xpc平台实现了对某型大柔性多体结构卫星系统的半实物仿真试验开发。试验过程中,对xpc目标进行了二次开发,在星载计算机硬件不成熟时,采用一台xpc目标机来实现其快速控制原型,另一台目标机模拟星载计算机外... 详细信息

介绍了xpc实时目标环境,借助xpc平台实现了对某型大柔性多体结构卫星系统的半实物仿真试验开发。试验过程中,对xpc目标进行了二次开发,在星载计算机硬件不成熟时,采用一台xpc目标机来实现其快速控制原型,另一台目标机模拟星载计算机外部实时环境,由一台xpc宿主机分别控制两台目标机保证仿真时钟同步。在快速控制原型的基础上逐步地引入实物部件从而实现半实物仿真系统的构建。整个卫星地面半实物仿真系统的开发过程是一种基于模型的系统设计思想,实验结果证明了方法的有效性。

关键词： xpc 半实物仿真大柔性多体结构星载计算机系统设计

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