Metastasis of Neuroendocrine Tumors Are Characterized by Increased Cell Proliferation and Reduced Expression of the ATM Gene 英文参考文献.docVIP

下载本文档

3
0
约3.4万字
约 8页
2017-05-12 发布于上海
举报
版权申诉

Metastasis of Neuroendocrine Tumors Are Characterized by Increased Cell Proliferation and Reduced Expression of the ATM Gene 英文参考文献.doc

1、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。。
2、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
3、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
6、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
7、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Metastasis of Neuroendocrine Tumors Are Characterized by Increased Cell Proliferation and Reduced Expression of the ATM Gene 英文参考文献

MetastasisofNeuroendocrineTumorsAreCharacterized byIncreasedCellProliferationandReducedExpression oftheATMGene JeeyunLee1.,ChangOhkSung2.¤,EuiJ.Lee3,In-GuDo4,Hee-CheolKim5,SeongHyeonYoon5 ,Woo YongLee5,HoKyungChun5,Kyoung-MeeKim2*,YoungSukPark1* 1DivisionofHematology-Oncology,DepartmentsofMedicine,SungkyunkwanUniversitySchoolofMedicine,Seoul,Korea,2Pathology,SungkyunkwanUniversitySchool ofMedicine,Seoul,Korea,3ResearchInstitute,IncheonSt.MaryHospital,CatholicUniversityofKorea,Seoul,Korea,4SamsungCancerResearchInstitute,Sungkyunkwan UniversitySchoolofMedicine,Seoul,Korea,5Surgery,SamsungMedicalCenter,SungkyunkwanUniversitySchoolofMedicine,Seoul,Korea Abstract Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare group of tumors with a wide spectrum of clinicalbehavior.However,therearenoknownclinicallyrelevantbiomarkerstopredictmetastasis. Experimental Design: To investigate differential gene expression signatures of metastatic vs non-metastatic NETs, we studied cell cycle regulatory genes in 19 metastatic and 22 non-metastatic colorectal NETs by PCR arrays. Immunohistochemistry (IHC) and quantitative real-time RT-PCR were performed to verify the results and another set of 38GEP-NETswerefurtherstudiedforvalidation. Results:WefirstdelineatedsixcandidategenesformetastasisincludingATM,CCND2,RBL2,CDKN3,CCNB1,andGTSE1 .ATM wasnegativelycorrelatedwithmetastaticNETs(p,0.001)withmorethan2-foldchangecomparedtonon-metastaticNETs. OverexpressionofATMproteinbyIHCwasstronglycorrelatedwithhighATMmRNAlevelsandlowKi-67labelingindex. Patients with ATM-negativity by IHC showed significantly decreased overall survival than patients with ATM-positivity (medianOS,metastaticvsnon-metastaticNETs;2.7yearsvsnotreached;p=0.003)and85.7%ofmetastaticNETswereATM- negative.InanothervalidationsetofGEP-NETs,decreasedmRNAofATMgenewasassociatedwithmetastasisandremained significant(p =0.023). Conclusions: ATM down-regulation was strongly associated with metastatic NETs when com