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Efficiency of olaparib in colorectal cancer patients with an alteration of the homologous repair protein

World Journal of Gastroenterology 2016年第48期22卷 10680-10686页

作者： Francois Ghiringhelli Corentin Richard Sandy Chevrier Frédérique Végran.Romain Boidot Department of Medical Oncology Center GF Leclerc21000 DijonFrance Platform of Transfer in Oncology Center GF Leclerc21000 DijonFrance INSERM UMR866 21000 DijonFrance University of Bourgogne Franche Comte 21000 DijonFrance

Precision medicine is defined by the administration of drugs based on the tumor's particular genetic characteristics. It is developing quickly in the field of cancer therapy. For example, KRAS, NRAS and BRAF genetic testing demonstrates its efficiency for precision medicine in colorectal cancer(CRC). Besides for these well-known mutations, the purpose of performing larger genetic testing in this pathology is unknown. Recent reports have shown that using the poly ADP ribose polymerase(PARP) inhibitor olaparib in patients with homologous repair enzyme deficiency gave positive clinical results in breast, ovarian and prostate cancers. We have reported here the cases of 2 patients with multi-treated metastatic CRC who underwent somatic and constitutional exome analyses. The analyses revealed a loss of function mutation in a homologous repair enzyme resulting in the loss of heterozygosity for both patients(Check2 for the first patient and RAD51 C for the second one). Both patients were treated with off-label usage of olaparib. While the first patient showed clinical benefit, reduction of carcinoembryonic antigen tumor marker and radiologic response, the second patient quickly presented a progression of the tumor. Additional genetic analyses revealed a frameshift truncating mutation of the TP53BP1 gene in the patient who progressed. Interestingly, deficiency in TP53BP1 was previously described to confer resistance to olaparib in mice breast cancer models. Our findings suggest that exome analysis may be a helpful tool to highlight targetable mutations in CRC and that olaparib may be efficient in patients with a homologous repair deficiency.

关键词： Colorectal cancer Exome analysis Genetic aberrations Homologous repair deficiency Precision medicine

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Conversion of Existing Roundabouts into Turbo-Roundabouts： Case Studies from Real World

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Journal of Civil Engineering and Architecture 2012年第8期6卷 953-962页

作者： Orazio Giuffrè Marco Guerrieri Anna gran. Department of Civil Environmental Aerospace Materials Engineering Università degli Studi di Palermo Palermo90128 Italy

Compared with roundabouts the main advantages of turbo-roundabouts are the reduction in the number of potential conflicting points and the lower speed of vehicles passing through the intersection, they both can improve safety conditions at the .junction. Moreover, the physical delimitation among lanes limits the side-by-side accident risk. These aspects make turbo-roundabouts more appropriate than roundabouts when a higher level of safety has to be guaranteed, particularly in presence of relevant pedestrian and two-wheels traffic volumes. The present paper has three main objectives：（1） to discuss general design criteria and functional principles of turbo roundabouts, （2） to give the geometric design principles of the central island and circulating lanes and （3） to present three case studies from real world concerning the conversion of existing roundabouts into turbo roundabouts.

关键词： Roundabout turbo roundabout capacity.

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Helicobacter pyloripromote gastric cancer cells invasion through a NF-κB and COX-2-mediated pathway

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World Journal of Gastroenterology 2005年第21期11卷 3197-3203页

作者： Chun-YingWu Chau-JongWang Chi-ChuanTseng Hsiao-PingChen Ming-ShingWu Jaw-TownLin HiroyasuInoue gran.HumChen GraduateInstituteofClinicalMedicine CollegeofMedicineNationalTaiwanUniversityTaiwanChina InstituteofBiochemistry CollegeofMedicineChung-ShanMedicalUniversityTaiwanChina DivisionofGastroenterology DepartmentofInternalMedicineNationalTaiwanUniversityHospitalTaiwanChina DivisionofGastroenterology DepartmentofInternalMedicineNationalTaiwanUniversityHospitalTaiwanChina DepartmentofPharmacology NationalCardiovascularCenterResearchInstituteJapan

AIM: To examine the effects of Helicobacter pylori(Hpylori) infection on the invasiveness of gastric cancer cells,and to elucidate its mechanism. METHODS: Gastric carcinoma cells, MKN-45, were incubated with CagA-positive H pylori, and cell invasion was determined by Matrigel *** expression of matrix metallopr-oteinase-9 (MMP-9),vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were assessed by Western-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and β-galactosidase activities. Lastly,the proteinDNA interaction was confirmed by an electrophoretic mobility shift assay. RESULTS: The current studies showed that: (1) incubation of CagA-positive H pylori with MKN-45 cells significantly promotes gastric cancer cells invasion, and this effect is attenuated by pre-treatment with NS-398, a COX-2 inhibitor, or PDTC,a nuclear factor κB (NF-κB) inhibitor;(2) the induction of MKN-45 cells invasion by Hpylori is associated with increases in COX-2, MMP-9, and VEGF protein expression, and co-incubation of NS-398 or PDTC significantly reduces these effects;(3) H pylori infection transactivates COX-2 promoter activity and increases the binding of NF-κB to this promoter. CONCLUSION: Our data demonstrate that H pylori infection promotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-κB and COX-2 mediated pathway, as COX-2 or NF-κB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.

关键词： H pylori Gastric cancer Invasion MMP-9 VEGF COX-2 NF-κB

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世界上首例小肠与肝脏同时移植获得成功

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浙江医学情报 1991年第2期3卷 46-47页

作者： gran.D 高惠荣

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原料油组成对Pt—Re—S／Al2O3—Cl重整催化剂选择性的影响

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石油炼制译丛 1990年第2期 26-30页

作者： gran.JM 胡云林

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急性冠脉综合征的危险分层和治疗决策制定

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美国医学会杂志（中文版） 2001年第4期20卷 208-210页

作者： Ohma EM gran.CB Division of Cardiology Department of Medicine and Department of Community and Family Medicine Duke Clinical Research Institute Duke University Medical Center Durham NC

近年来急性冠脉综合征的治疗取得了长足的进步,正像80年代急性心肌梗死(MI)的治疗进展.当时纤维蛋白溶解和阿司匹林治疗显著降低了死亡率1.虽然这些治疗首先用于所有可疑MI的患者1,但ST段抬高或左束支阻滞的患者(即使不是全部)也获得了... 详细信息

近年来急性冠脉综合征的治疗取得了长足的进步,正像80年代急性心肌梗死(MI)的治疗进展.当时纤维蛋白溶解和阿司匹林治疗显著降低了死亡率1.虽然这些治疗首先用于所有可疑MI的患者1,但ST段抬高或左束支阻滞的患者(即使不是全部)也获得了极大的疗效2.此后,在普遍使用链激酶和组织纤溶酶原激活剂(tPA)治疗闭塞性冠状动脉(GUSTO-Ⅰ)的试验中,发现加速的tPA优于链激酶,30天的死亡率相对下降14%3.死亡率模式提示tPA治疗(不依赖其他因素)预后较好,该结果在所有亚组中均如此,与绝对危险性无关4.既然未发现不同的治疗效果,这说明几乎所有MI患者会从tPA治疗获益.

关键词：急性冠状动脉综合征治疗危险性

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融合模糊增强与改进Canny的植物叶脉边缘提取

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光电子．激光 2018年第11期29卷 1251-1258页

作者：任克强张静然江西理工大学信息工程学院江西赣州341000

针对植物叶脉边缘提取存在的问题,提出一种图像模糊增强与改进Canny算子相结合的叶脉边缘提取方法。该方法首先构造分段模糊隶属度函数对高低灰度进行不同处理,然后通过模糊增强函数来增强叶脉两侧邻接区域灰度对比度,最后对增强图像采... 详细信息

针对植物叶脉边缘提取存在的问题,提出一种图像模糊增强与改进Canny算子相结合的叶脉边缘提取方法。该方法首先构造分段模糊隶属度函数对高低灰度进行不同处理,然后通过模糊增强函数来增强叶脉两侧邻接区域灰度对比度,最后对增强图像采用改进Canny算子提取叶脉边缘。改进Canny算子根据像素点与局部像素的均值差来自适应的应用高斯滤波,以减小滤波对边缘的平滑影响;采用Prewitt模板计算梯度幅值和方向,以减小噪声对梯度计算的影响;采用线性插值技术实现全向非极大值抑制,以更准确的实现边缘细化。实验结果表明,本文方法在低照度叶片和光照不均叶片下提取叶脉边缘的PSNR分别为51.136 2dB和50.217 4dB,与传统边缘提取方法及相关文献相比,本文方法对边界模糊性不敏感,可以更加有效地提取完整精细的叶脉边缘。

关键词：叶脉边缘提取模糊增强改进Canny算子隶属度函数自适应高斯滤波

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QTS岩石分类法及其在布拉格应用的效果

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隧道译丛 1993年第11期 22-26页

作者： gran.J 张玉珍

本文介绍的ＱＴＳ法是由捷克斯洛代克科学研究所所提出的，在布拉格地铁初次应用即获得很好的效果。采用此法的主要原因是想了解裂隙带岩石稳定性及地下水的影响，曾试用过多种物理和数学模型，并曾找出ＱＴＳ法与不同直径，岩石条件，... 详细信息

本文介绍的ＱＴＳ法是由捷克斯洛代克科学研究所所提出的，在布拉格地铁初次应用即获得很好的效果。采用此法的主要原因是想了解裂隙带岩石稳定性及地下水的影响，曾试用过多种物理和数学模型，并曾找出ＱＴＳ法与不同直径，岩石条件，施工进度，开挖方式之间的关系。经过１５年的实践证明此法可靠。ＱＴＳ法已被捷克斯洛代克国家标准所采用。

关键词： QTS法岩石分类隧道

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In-vivo validation of fast spectral velocity estimation techniquespreliminary results

In-vivo validation of fast spectral velocity estimation tech...

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2008 IEEE International Ultrasonics Symposium

作者： Kristoffer L.Hansen Fredrik gran.Mads M.Pedersen Jφrgen A.Jensen Michael B.Nielsen University Hospital of Copenhagen

＜正＞Background,Motivation and Objective A common way of displaying blood velocity is to estimate the power spectral density（PSD）as a function of time yielding a *** usual method to estimate PSD is by using the ave...

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HEART RATE VARIABILITY DURING HIGH-INTENSITY EXERCISE

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Journal of Systems Science & Complexity 2013年第1期26卷 104-116页

作者： SARMIENTO Samuel GARCIA-MANSO Juan Manuel MARTIN-GONZALEZ Juan Manuel VA-AMONDE Diana CALDERóN Javier da SILVA-GRIGOLETTO Marzo Edir Department of Physical Education University of Las Palmas de Gran Canaria Spain. Physics Department University of Las Palmas de Gran Canaria Spain. Department of Morphological Sciences School of Medicine University of Cdrdoba Spain. Physical Activity Sciences Faculty Polytechnic University of Madrid Spain. Andalusian Centre of Sports Medicine Cdrdoba Spain.

The aim of this paper is to describe and analyse the behaviour of heart rate variability(HRV)during constant-load,high-intensity exercise using a time frequency analysis(Wavelet Transform).Eleven elite cyclists took part in the study(age:18.6±3.0 years;VO_(2max):4.88±0.61 litres·min^(-1)).Initially,all subjects performed an incremental cycloergometer test to determine load power in a constant load-test(379.55±36.02 W;89.0%).HRV declined dramatically from the start of testing(p<0.05).The behaviour of power spectral density within the LF band mirrored that of total energy,recording a significant decrease from the outset LF peaks fell rapidly thereafter,remaining stable until the end of the ***-VHF fell sharply in the first 20 to 30 *** relative weighting(%) of HF-VHF was inverted with the onset of fatigue,[1.6%at the start,7.1(p<0.05) at the end of the first phase,and 43.1%(p<0.05) at the end of the test].HF-VHF_(peak) displayed three phases:a moderate initial increase,followed by a slight fall,thereafter increasing to the end of the *** LF/HF-VHF ratio increased at the start,later falling progressively until the end of the first phase and remaining around minimal values until the end of the test.

关键词： Cycling heart rate variability wavelet.

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