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| 1 | Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma显示文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments. | Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen | 2021 | Frontiers of Medicine2021，15，2： | 3 |
| 2 | MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors显示文摘 | Liu Xi Sempere Lorenzo F Ouyang Haoxu Memoli Vincent A Andrew Angeline S Luo Yue Demidenko Eugene Korc Murray Shi Wei Preis Meir Dragnev Konstantin H Li Hua DiRenzo James Bak Mads Freemantle Sarah J Kauppinen Sakari Dmitrovsky Ethan | 2010 | Journal of Clinical Investigation2010，，4： | 3 |
| 3 | 紫杉醇局部治疗抑制猪静脉桥新生内膜形成和增厚的实验研究显示文摘目的 :局部药物治疗是一个很好的防治静脉桥病变的策略。本研究用抗细胞增殖药物紫杉醇处理大隐静脉桥后植入猪的颈动脉 ,以观察紫杉醇的抗细胞增殖作用在抑制静脉桥内膜平滑肌细胞增殖、迁移导致内膜形成和增厚的效果。方法 :将 10头猪的 2 0只大隐静脉桥分为两组。治疗组 :将大隐静脉桥 10只置于含有 10 μmol/L浓度的紫杉醇溶液中 (先用该溶液灌洗 )浸泡 1h后植入猪的颈动脉 ,紫杉醇是溶解在 2 5 μl/L的无水酒精中 ,对照组 10只大隐静脉桥置于单纯的酒精中浸泡。 4周后取开放的静脉桥进行组织学分析。结果 :①治疗组静脉桥新生内膜面积 (1 5 9± 0 95 )mm2 ,对照组新生内膜面积高达 (2 43± 1 3 5 )mm2 ,治疗组显著低于对照组 ,两组比较有非常显著的差异 ,P <0 0 1;②治疗组内膜平滑肌细胞密度均值为 (3 681± 193 5 ) /mm2 ,对照组为 (4 60 7± 1993 ) /mm2 ,两组比较有显著性差异 ,P <0 0 5 ;中膜平滑肌细胞密度均值治疗组 (2 13 9± 73 4) /mm2 ,对照组(3 62 9± 3 2 0 7) /mm2 ,两组比较有显著性的差异 ,P <0 0 5。结论 :紫杉醇可显著抑制静脉桥内膜、中膜平滑肌细胞的增殖 ,抑制新生内膜的形成 ,证明紫杉醇可在防治静脉桥闭塞方面发挥独特作用。 | 吴隐雄 Martin H Chamberlain Thomas Johnson Jason L Johnson Andrew C Newby Gianni D Angelin Martin Oberhoff Karl K Karsch | 2003 | 中国循环杂志2003，18，6： | 2 |
| 4 | Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients With liver cirrhosis显示文摘 | Grace Lai‐Hung Wong Henry Lik‐Yuen Chan Christy Wing‐Hin Mak Stanley King‐Yeung Lee Zoe Man‐Yi Ip Andrew Ting‐Ho Lam Henry Wing‐Hang Iu Joyce May‐Sum Leung Jennifer Wing‐Yan Lai Angeline Oi‐Shan Lo Hoi‐Yun Chan Vincent Wai‐Sun Wong | 2013 | Hepatology2013，，5： | 1 |
| 5 | DNA repair polymorphisms modify bladder cancer risk:a multi-factor analytic strategy显示文摘 | Angeline S Andrew Margaret R | 2008 | Hum Hered2008，65，： | 1 |
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