老师标书医药卫生科研项目可行性报告

1、(省部共建项目利用目标区域捕获分子1、立项的背景技术研究大肠型和表型的关组修复 (省部共建项目利用目标区域捕获分子1、立项的背景技术研究大肠型和表型的关组修复 2、国内外现状和发展 Cancer肉 （K-RAS ，c-MYC，EGFR等） 等）3-5。而从癌前病变发展到癌的过程包括多种细胞通路包括 ， 行DNA 错配修复（mismatchrepair，MMR）DNA hMSH2 hMLH1公认并被写进了教科书12。有研究表明，多种 错误碱基的能力下降或缺乏，进而造成 DNA 不稳定性instability，MSI）与 差错（replication等）3-5。而从癌前病变发展到癌的过程包括多种细

2、胞通路包括 ， 行DNA 错配修复（mismatchrepair，MMR）DNA hMSH2 hMLH1公认并被写进了教科书12。有研究表明，多种 错误碱基的能力下降或缺乏，进而造成 DNA 不稳定性instability，MSI）与 差错（replicationerror，RER）13-17表明，DNA 错配修复缺陷的大肠肿瘤细胞对药物治疗更敏感18, 19MMR和 hMLH1）。新一代的研究为高通量获得大量突变信息提供了可能 序（Whole Genome Sequencing, WGS） ，总结对收集到的大肠癌患者的血液和肿瘤组织（Wolpin, B.M. and R.J. Mayer,

3、Systemic treatment of colorectal cancer. Gastroenterology, 2008. 134(5): p. 1296-310.Xu, A.G., et al., Colorectal ，总结对收集到的大肠癌患者的血液和肿瘤组织（Wolpin, B.M. and R.J. Mayer, Systemic treatment of colorectal cancer. Gastroenterology, 2008. 134(5): p. 1296-310.Xu, A.G., et al., Colorectal cancer in Guangdong P

4、rovince of China: a demographic and anatomic survey. World J Gastroenterol, 2010. 16(8): p. 960-5.Comprehensive molecular characterization of human colon and rectal cancer. Nature, 487(7407):p.330-Sadanandam, A., et al., A colorectal cancer classification phenotypeandresponsestotherapy.NatMed,2013.1

5、9(5):p.619-t tes Aaltonen, L.A., et al., Clues to the pathogenesis 260(5109):p.812-milial colorectal cancer. Science, Palles, C., et al., Germline ions affecting the s of POLE POLD1 e to colorectal adenomas and carcinomas. Nat Genet, 2013. 45(2): Parsons, D.W., et al., Colorectal cancer: ions in a s

6、ignalling pathway. Nature, 436(7052):p.Misale, S., et al., Emergence of KRAS ions and to anti-therapyincolorectalcancer.Nature,2012.486(7404):p.532-Ross, J.S., et al., Biomarker-based prediction of response to therapy for colorectal .AmJClinPathol,2010.134(3):p.478-Tougeron, D., et al., Effect of lo

7、w-frequency KRAS ions on the response to anti-iccolorectalcancer.AnnOncol,2013.24(5):p.1267-therapyincolorectalcancer.Nature,2012.486(7404):p.532-Ross, J.S., et al., Biomarker-based prediction of response to therapy for colorectal .AmJClinPathol,2010.134(3):p.478-Tougeron, D., et al., Effect of low-

8、frequency KRAS ions on the response to anti-iccolorectalcancer.AnnOncol,2013.24(5):p.1267-mismatch-repair-deficientcellstobulky2006.103(42):p.15359-ercalators.ProcAcadSciUSJenkins, M.A., et al., Cancer risks for mismatch repair gene muion carriers: a population-based early onset case-family study. C

9、lin Gastroenterol Hepatol, 2006. 4(4): Park, J.G., et al., Germ line ions of mismatch repair genes in hereditary colorectal atients with small bowel ernational Society HereditaryTumoursCollaborativeStudy.ClinCancerRes,2006.12(11Pt1):p.3389-Shin, K.H., et al., hMLH1 in hereditary ysis of promoters of

10、 mismatch repair genes hMSH2 is colorectal cancer and early onset colorectal patients: identification of three novel germ-line ions in promoter of the hMSH2 CancerRes,2002.62(1):p.38-Liu, W., et al., ionsin AXIN2 cause colorectal cancer with defective mismatch repair activatingbeta-CFsignalling.NatG

11、enet,2000.26(2):p.146-Leung, S.Y., et al., Microsa lite instability and ion of DNA mismatch repair genes gliomas.AmJPathol,1998.153(4):p.1181-Liu, B., et al.,Mismatch repair gene defects in instability.NatGenet,1995.9(1):p.48-olorectal cancers with microsa Pogue-Geile, K., et al., Defective mismatch

12、 repair and benefit from bevacizumab for cancer:findingsfromNSABPC-08.JCancerInst,2013.105(13):p.989-Sinicrope, F.A., et al., DNA mismatch repair us and colon cancer recurrence and in clinical trials of 5-fluorouracil-based adjuvant therapy. J p.863-Cancer Inst, 2011. Watson, I.R., et al., Emerging

13、patterns of somatic ions in cancer. Nat Rev Genet, 14(10):p.703-Roach, J.C., et ysis of genetic inheritance in a family quartet by whole-sequencing.Science,2010.328(5978):p.636-Sanders, S.J., et al., De novo ions revealed by whole-exome sequencing are tedutism.Nature,2012.485(7397):p.237-Huang, X.F.

14、, et ed exome sequencing identified novel USH2A ions in syndromefami s.PLoSOne,2013.8(5):p.1. 123ATR C123C46RC6B1、族史、临床检查结果等组提取（按照常规方法进行Hiseq2000 ）Sanger析：的进度安排2014.01-2015.012015.122016.01-表进度安排2014.01-2015.012015.122016.01-表可行性分析：该项目的设计以申请者前期的工作为基础，具有较好的可行在方法学上的创新表现将首次设计特异组修复相关分子捕获SCI23) 21在方法学上的创

15、新表现将首次设计特异组修复相关分子捕获SCI23) 21）和技术标准现状及预期的。（PLoSONE8(5):序深度（图 1:10.1371/journalpone.00638322）课题申及主要参研究基础（已有的研究开发经历，科技成科研条件与研究开发队伍现状等53个病区，44临床科室、10016933、18 麻醉学9 项目申请温州973 2）课题申及主要参研究基础（已有的研究开发经历，科技成科研条件与研究开发队伍现状等53个病区，44临床科室、10016933、18 麻醉学9 项目申请温州973 项目（ ，3）及课题重要参的相关工作基础与，医2003 年”551 20 等 5 项，作为副主编编

16、写的中西医结合肛肠病治疗学一书。临床工作近 300 例/（均为通讯作者1辣椒素对结肠癌鼠皮下移植瘤的抑制作用及机制，中华肿瘤杂志，25-Fu SW480 4VEGF-C 和 FLT-4 学刊 等 5 项，作为副主编编写的中西医结合肛肠病治疗学一书。临床工作近 300 例/（均为通讯作者1辣椒素对结肠癌鼠皮下移植瘤的抑制作用及机制，中华肿瘤杂志，25-Fu SW480 4VEGF-C 和 FLT-4 学刊 课题重要参博士后，2006 作，取得了部分成绩。在Cell Stem Cell、Human ion、Scientific ReportsMolecular 文章 17 篇。是多个国际杂志（Mo

17、lecular CurrentEyeResearchnJournaloflmology、Medical1.的 R33C该研究首次发现该蛋白跨膜区以外的突变可以导致白内障。首次发现 R116H 突变使-A 和2.在201151.的 R33C该研究首次发现该蛋白跨膜区以外的突变可以导致白内障。首次发现 R116H 突变使-A 和2.在20115上，首次利用凝胶阻滞实验证明了在人类胚胎干细胞中 NANOG SMADs 404bp380-+24)NANOG主文1、 Yihua Zhu, Jianfu Zhuang, Xianglian Ge, Xiao Zhang, Zheng Wang, & Fen

18、g Gu，Identifcation of a Novel Sun, ionp.I240Tin a Family with Congenital Nystagmus ， the FRMD7 2、 Xiu-Feng :10.1038/srep03084 （影响因子，2.9，通讯作者Xiang,Jie Chen,Dong-JunXing,NaHuang,Min,1、 Yihua Zhu, Jianfu Zhuang, Xianglian Ge, Xiao Zhang, Zheng Wang, & Feng Gu，Identifcation of a Novel Sun, ionp.I240Tin

19、a Family with Congenital Nystagmus ， the FRMD7 2、 Xiu-Feng :10.1038/srep03084 （影响因子，2.9，通讯作者Xiang,Jie Chen,Dong-JunXing,NaHuang,Min, Feng Gu,Yi Tong, Chi-Pui Pang, Jia Qu,Zi-Bing ed SequencingIdentifiedNovelUSH2Aionsin Usher SyndromePLoSONE8(53、 Ren-He Xu, Tori L. Barron, Feng Gu, Sierra Root, nn Pe

20、ck,Guangjin Pan, Junying Yu, Jessica Antosiewicz-Bourget, Shulan Ron Stewart, and James A. Thomson. NANOG is a ediated SMAD signaling in human ESCs. Cell Stem 2008,3(2):196-206. （4、 Zhang,Baojian Zhao, Siquan Zhu,Shan Feng,Yong-bin Yan, Shangzhi and Xu Ma. A novel ion in AlphaA-crystallin (CRYAA) au

21、tosomal dominant congenital cataract in a large family. ion2008;29(5):769. （5、 Feng Gu,Hong Zhai, Dan Li, Luxin Zhao, Chao li, Shangzhi Huang and Ma. A novel ion in rinsic protein of the lens gene sautosomaldominantcataractinafamily.Molecular2007;13:1651-1656. （6、 Wei Liu*, Feng Gu*, Jian Ji, Duan novel nonsen