胰腺癌相关免疫原性膜抗原SLP-2和TOM40的鉴定和初步研究
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摘要
研究背景:
胰腺癌是一种起病隐匿、进展迅速、预后极差的消化道高度恶性肿瘤。早期诊断是胰腺癌以手术为主、联合运用多种方法的综合治疗体系的关键所在,血清肿瘤标记物的筛查是胰腺癌早期诊断研究的重要内容之一。本课题组提出了以肿瘤免疫理论为基础采用胰腺癌相关免疫原性膜抗原抗体作为胰腺癌诊断标记物的新构想,并设计出了胰腺癌相关免疫原性膜抗原的筛查策略。
为了筛查胰腺癌相关免疫原性膜抗原进而确定胰腺癌血清抗体作为肿瘤标记物,前期实验通过运用“胰腺癌细胞株膜蛋白-免疫印记杂交-蛋白质组学”筛查方式发现,相比于正常人和慢性胰腺炎病人,胰腺癌病人体内特异性存在SLP-2和TOM40蛋白的血清抗体,从而提出SLP-2和TOM40可能为人胰腺癌相关免疫原性膜抗原,其血清抗体有可能被用作胰腺癌的肿瘤标记物,因此有必要在人胰腺癌组织中对SLP-2和TOM40的表达进行研究。
研究目的:
对人胰腺癌组织中SLP-2和TOM40的表达进行研究,从基因(转录)和蛋白(翻译)两个水平、细胞和组织两层面获取SLP-2和TOM40作为胰腺癌相关免疫原性膜抗原存在的客观证据;对SLP-2和TOM40进行生物信息学分析,在三株常用胰腺癌细胞系中对SLP-2和TOM40进行定位和相对表达强度研究,构建SLP-2基因RNA干扰的表达载体pGPU6/GFP/Neo-SLP-2-shRNA,为在胰腺癌中进一步开展SLP-2的研究打下一定基础。
研究方法:
采用Real time PCR和Western blot研究SLP-2和TOM40在胰腺癌中的表达情况,同时采用人胰腺癌组织芯片(TMA)进行SLP-2和TOM40的免疫组化染色,从组织水平获取SLP-2和TOM40作为人胰腺癌免疫原性膜抗原存在的客观证据;运用生物信息学网络平台NCBI、ASTD、Oncomine Research Platform、Gene Ontology、UCSCGenome Browser以及本地生物信息学分析软件ESvPred3D、ClustalX、TreeView对SLP-2和TOM40进行蛋白进化分析、基因可变剪接分析、电子表达谱分析、转录调控分析,同时进行三维结构预测和miRNA作用位点预测并分析SLP-2和TOM40可能的B细胞表位和CTL表位;对胰腺癌细胞株AsPC-1、BxPC-3、PANC-1进行SLP-2和TOM40的细胞免疫荧光染色,利用激光共聚焦显微镜研究其在胰腺癌细胞株中的相对表达强度和细胞定位;采用pGPU6/GFP/Neo构建用于SLP-2 RNA干扰研究的表达载体pGPU6/GFP/Neo-SLP-2-shRNA。
实验结果:
1.Real time PCR检测显示SLP-2和TOM40基因在10例正常胰腺组织和10例胰腺癌组织均存在表达,相对于正常胰腺组织,TOM40有高表达趋势。
2.Western blot检测显示SLP-2和TOM40蛋白在10例正常胰腺组织和10例胰腺癌组织均存在表达;含75例胰腺导管腺癌的组织芯片免疫组化检测显示SLP-2和TOM40在胰腺癌细胞中存在表达,并且相对于正常胰腺组织,SLP-2和TOM40有高表达趋势。
3.蛋白进化分析构建了SLP-2和TOM40系统进化树;基因调控分析提示SLP-2可能受到CEBP、ELK1等转录因子的调控,TOM40可能受到CDPCR3、PAX5等转录因子的调控;miRNA预测分析了可能调控SLP-2和TOM40的miRNA;三级结构预测获得了SLP-2可能的三级结构;抗原表位预测分析提示氨基酸序列“SSGSSRD”和“TSTSRSS”可能为SLP-2和TOM40较合理的B细胞表位,而氨基酸序列“ILEPGLNIL”和“TLNNWLATV”等可能为SLP-2和TOM40的CTL细胞表位。
4.胰腺癌细胞株免疫荧光染色激光共聚焦显微镜观察显示,SLP-2主要位于胰腺癌细胞株AsPC-1、BxPC-3、PANC-1的细胞质,三株胰腺癌细胞株SLP-2的相对表达水平存在显著差异,其中PANC-1表达最高,而AsPC-1表达最低;TOM40主要位于胰腺癌细胞株AsPC-1、BxPC-3、PANC-1的细胞质,三株胰腺癌细胞株TOM40的相对表达水平存在显著差异,以PANC-1表达最高,而AsPC-1表达最低。
5.预测了SLP-2 RNA干扰靶位点,挑选设计出了4个可能的干扰序列,利用其完成SLP-2RNA干扰载体pGPU6-GFP-Neo-SLP-2-shRNA的构建并成功转染胰腺癌细胞株SW1990。
结论:
SLP-2和TOM40在人胰腺癌组织中呈广泛性表达趋势,而病人血清内特异性存在其抗体,提示SLP-2和TOM40为人胰腺癌相关免疫原性膜抗原并在人胰腺癌中可能具有一定的代表性,为以SLP-2和TOM40血清抗体作为胰腺癌肿瘤标记物的新策略提供了一定的实验证据支持。
BACKGROUND
The human pancreatic cancer is one of the most deadly malignancies with silence onset,rapid progress and poor prognosis.Early diagnosis of pancreatic cancer plays a central role in the comprehensive therapy system which combined the surgery and other therapies such as chemotherapy and radiotherapy.The screening of serum tumor marker was considered to be one of the most hopeful methods to make a progress in pancreatic diagnosis research.
Our lab presented a new concept to detect pancreatic cancer which planed to use the antibodies of immunogenic associated membrane antigens,and also presented the concept of pancreatic cancer associated immunogenic membrane antigens and designed a new screening strategy for the pancreatic cancer associated immunogenic membrane antigens.
After the previous work of our research team which were based on the pancreatic cancer cell line extracted membrane proteins,Western blot and proteomics,the IgG of SLP-2 and TOM40 were detected in the serum of pancreatic cancer patient without in the normal persons and chronic pancreatitis patients,so the antibodies of SLP-2 and TOM40 were considered to have potential diagnosis value in pancreatic cancer,and the expression condition of SLP-2 and TOM40 in pancreatic cancer are needed to be further investigated.
OBJECTIVE
To study the expression of SLP-2 and TOM40 in human pancreatic cancer both in the transcript level and translation level,and to identify the SLP-2 and TOM 40 as pancreatic cancer associated immunogenic membranes,and also conduct some initial study of these two proteins which are associated with pancreatic cancer and do some basic work for the future investigation of the 2 proteins in pancreatic cancers.
METHODS
The Real time PCR,Western blot and immunohistochemistry of human pancreatic cancer tissue microarray were used to detect the expression of SLP-2 and TOM40 in different levels of human pancreatic cancer.Bioinformatics analysis was conducted to both gene and protein of SLP-2 and TOM40 by the online database such as NCBI、 ASTD、Oncomine Research Platform、Gene Ontology、UCSC Genome Browser,and also the local bioinformatics software such as ESyPred3D,ClustalX,and TreeView.etc.The analysis included the evolution of protein,the gene alternative splicing and transcript, electronic expression spectrum,the prediction included miRNA and the antigen epitope of B cell and cytotoxic T lymphatic cell.The immunologic fluorescence cytochemistry method was conducted to the pancreatic cell line AsPC-1,BxPC-3,PANC-1 and the confocal laser scanning microscopy was used to identify the position of the SLP-2 and TOM40 and also the related expression levels in the 3 pancreatic cell lines.The vector pGPU6/GFP/Neo was used to construct the SLP-2 RNA interfering vector.
RESULTS
1.Real time PCR detected the expression of SLP-2 and TOM 40 in both 10 cases human pancreatic caner and 10 cases normal human pancreatic tissue,and the TOM40 had high expression level in pancreatic cancer tissue compared to the normal pancreatic tissue.
2.Western blot detected the expression of SLP-2 and TOM40 in both 10 cases human pancreatic caner and 10 cases normal human pancreatic tissue;the immunohistochemistry of human pancreatic tissue microarray indicated the expression of SLP-2 and TOM40 in pancreatic cancer,the SLP-2 and TOM40 had high expression levels in pancreatic cancer tissues compared to the normal pancreatic tissues.
3.The protein evolution trees of SLP-2 and TOM40 was constructed,and the transcript factor prediction analysis indicated that the SLP-2 might be regulated by CEBP and ELK1 ect,and the TOM40 might be regulated by the CDPCR3,PAX5 etc.The miRNA prediction presented the miRNA which might regulated the SLP-2 and TOM40,and the prediction 3-D structure of SLP-2 was made,and the antigen epitope of B cell and cytotoxic T lymphatic cell were predicted and presented.
4.The confocal laser scanning microscopy observation of pancreatic immunologic fluorescence cytochemistry indicated that both SLP-2 and TOM40 was expressed in the cytoplasm of pancreatic cancer AsPC-1,BxPC-3 and PANC-1.The PANC-1 cell line had the highest expression level of both SLP-2 and TOM40,and the AsPC-1 cell line had the lowest expression level.
5.The SLP-2 RNA interfering vector pGPU6-GFP-Neo-SLP-2-shRNA was constructed and the pancreatic cell line SW1990 was transfected successful.
CONCLUSIONS
1.SLP-2 and TOM40 were identified as the human pancreatic cancer associated immunogenic membrane antigens.
2.The SLP-2 and TOM40 proteins mainly localized in the cytoplasm of pancreatic cell line AsPC-1,BxPC-3 andPANC-1,the expression of both SLP-2 and TOM40 had significant difference in these three pancreatic cell line,the PANC-1 had the highest expression level but the AsPC-1 had the lowest one.
胰腺癌是一种起病隐匿、进展迅速、预后极差的消化道高度恶性肿瘤。早期诊断是胰腺癌以手术为主、联合运用多种方法的综合治疗体系的关键所在,血清肿瘤标记物的筛查是胰腺癌早期诊断研究的重要内容之一。本课题组提出了以肿瘤免疫理论为基础采用胰腺癌相关免疫原性膜抗原抗体作为胰腺癌诊断标记物的新构想,并设计出了胰腺癌相关免疫原性膜抗原的筛查策略。
为了筛查胰腺癌相关免疫原性膜抗原进而确定胰腺癌血清抗体作为肿瘤标记物,前期实验通过运用“胰腺癌细胞株膜蛋白-免疫印记杂交-蛋白质组学”筛查方式发现,相比于正常人和慢性胰腺炎病人,胰腺癌病人体内特异性存在SLP-2和TOM40蛋白的血清抗体,从而提出SLP-2和TOM40可能为人胰腺癌相关免疫原性膜抗原,其血清抗体有可能被用作胰腺癌的肿瘤标记物,因此有必要在人胰腺癌组织中对SLP-2和TOM40的表达进行研究。
研究目的:
对人胰腺癌组织中SLP-2和TOM40的表达进行研究,从基因(转录)和蛋白(翻译)两个水平、细胞和组织两层面获取SLP-2和TOM40作为胰腺癌相关免疫原性膜抗原存在的客观证据;对SLP-2和TOM40进行生物信息学分析,在三株常用胰腺癌细胞系中对SLP-2和TOM40进行定位和相对表达强度研究,构建SLP-2基因RNA干扰的表达载体pGPU6/GFP/Neo-SLP-2-shRNA,为在胰腺癌中进一步开展SLP-2的研究打下一定基础。
研究方法:
采用Real time PCR和Western blot研究SLP-2和TOM40在胰腺癌中的表达情况,同时采用人胰腺癌组织芯片(TMA)进行SLP-2和TOM40的免疫组化染色,从组织水平获取SLP-2和TOM40作为人胰腺癌免疫原性膜抗原存在的客观证据;运用生物信息学网络平台NCBI、ASTD、Oncomine Research Platform、Gene Ontology、UCSCGenome Browser以及本地生物信息学分析软件ESvPred3D、ClustalX、TreeView对SLP-2和TOM40进行蛋白进化分析、基因可变剪接分析、电子表达谱分析、转录调控分析,同时进行三维结构预测和miRNA作用位点预测并分析SLP-2和TOM40可能的B细胞表位和CTL表位;对胰腺癌细胞株AsPC-1、BxPC-3、PANC-1进行SLP-2和TOM40的细胞免疫荧光染色,利用激光共聚焦显微镜研究其在胰腺癌细胞株中的相对表达强度和细胞定位;采用pGPU6/GFP/Neo构建用于SLP-2 RNA干扰研究的表达载体pGPU6/GFP/Neo-SLP-2-shRNA。
实验结果:
1.Real time PCR检测显示SLP-2和TOM40基因在10例正常胰腺组织和10例胰腺癌组织均存在表达,相对于正常胰腺组织,TOM40有高表达趋势。
2.Western blot检测显示SLP-2和TOM40蛋白在10例正常胰腺组织和10例胰腺癌组织均存在表达;含75例胰腺导管腺癌的组织芯片免疫组化检测显示SLP-2和TOM40在胰腺癌细胞中存在表达,并且相对于正常胰腺组织,SLP-2和TOM40有高表达趋势。
3.蛋白进化分析构建了SLP-2和TOM40系统进化树;基因调控分析提示SLP-2可能受到CEBP、ELK1等转录因子的调控,TOM40可能受到CDPCR3、PAX5等转录因子的调控;miRNA预测分析了可能调控SLP-2和TOM40的miRNA;三级结构预测获得了SLP-2可能的三级结构;抗原表位预测分析提示氨基酸序列“SSGSSRD”和“TSTSRSS”可能为SLP-2和TOM40较合理的B细胞表位,而氨基酸序列“ILEPGLNIL”和“TLNNWLATV”等可能为SLP-2和TOM40的CTL细胞表位。
4.胰腺癌细胞株免疫荧光染色激光共聚焦显微镜观察显示,SLP-2主要位于胰腺癌细胞株AsPC-1、BxPC-3、PANC-1的细胞质,三株胰腺癌细胞株SLP-2的相对表达水平存在显著差异,其中PANC-1表达最高,而AsPC-1表达最低;TOM40主要位于胰腺癌细胞株AsPC-1、BxPC-3、PANC-1的细胞质,三株胰腺癌细胞株TOM40的相对表达水平存在显著差异,以PANC-1表达最高,而AsPC-1表达最低。
5.预测了SLP-2 RNA干扰靶位点,挑选设计出了4个可能的干扰序列,利用其完成SLP-2RNA干扰载体pGPU6-GFP-Neo-SLP-2-shRNA的构建并成功转染胰腺癌细胞株SW1990。
结论:
SLP-2和TOM40在人胰腺癌组织中呈广泛性表达趋势,而病人血清内特异性存在其抗体,提示SLP-2和TOM40为人胰腺癌相关免疫原性膜抗原并在人胰腺癌中可能具有一定的代表性,为以SLP-2和TOM40血清抗体作为胰腺癌肿瘤标记物的新策略提供了一定的实验证据支持。
BACKGROUND
The human pancreatic cancer is one of the most deadly malignancies with silence onset,rapid progress and poor prognosis.Early diagnosis of pancreatic cancer plays a central role in the comprehensive therapy system which combined the surgery and other therapies such as chemotherapy and radiotherapy.The screening of serum tumor marker was considered to be one of the most hopeful methods to make a progress in pancreatic diagnosis research.
Our lab presented a new concept to detect pancreatic cancer which planed to use the antibodies of immunogenic associated membrane antigens,and also presented the concept of pancreatic cancer associated immunogenic membrane antigens and designed a new screening strategy for the pancreatic cancer associated immunogenic membrane antigens.
After the previous work of our research team which were based on the pancreatic cancer cell line extracted membrane proteins,Western blot and proteomics,the IgG of SLP-2 and TOM40 were detected in the serum of pancreatic cancer patient without in the normal persons and chronic pancreatitis patients,so the antibodies of SLP-2 and TOM40 were considered to have potential diagnosis value in pancreatic cancer,and the expression condition of SLP-2 and TOM40 in pancreatic cancer are needed to be further investigated.
OBJECTIVE
To study the expression of SLP-2 and TOM40 in human pancreatic cancer both in the transcript level and translation level,and to identify the SLP-2 and TOM 40 as pancreatic cancer associated immunogenic membranes,and also conduct some initial study of these two proteins which are associated with pancreatic cancer and do some basic work for the future investigation of the 2 proteins in pancreatic cancers.
METHODS
The Real time PCR,Western blot and immunohistochemistry of human pancreatic cancer tissue microarray were used to detect the expression of SLP-2 and TOM40 in different levels of human pancreatic cancer.Bioinformatics analysis was conducted to both gene and protein of SLP-2 and TOM40 by the online database such as NCBI、 ASTD、Oncomine Research Platform、Gene Ontology、UCSC Genome Browser,and also the local bioinformatics software such as ESyPred3D,ClustalX,and TreeView.etc.The analysis included the evolution of protein,the gene alternative splicing and transcript, electronic expression spectrum,the prediction included miRNA and the antigen epitope of B cell and cytotoxic T lymphatic cell.The immunologic fluorescence cytochemistry method was conducted to the pancreatic cell line AsPC-1,BxPC-3,PANC-1 and the confocal laser scanning microscopy was used to identify the position of the SLP-2 and TOM40 and also the related expression levels in the 3 pancreatic cell lines.The vector pGPU6/GFP/Neo was used to construct the SLP-2 RNA interfering vector.
RESULTS
1.Real time PCR detected the expression of SLP-2 and TOM 40 in both 10 cases human pancreatic caner and 10 cases normal human pancreatic tissue,and the TOM40 had high expression level in pancreatic cancer tissue compared to the normal pancreatic tissue.
2.Western blot detected the expression of SLP-2 and TOM40 in both 10 cases human pancreatic caner and 10 cases normal human pancreatic tissue;the immunohistochemistry of human pancreatic tissue microarray indicated the expression of SLP-2 and TOM40 in pancreatic cancer,the SLP-2 and TOM40 had high expression levels in pancreatic cancer tissues compared to the normal pancreatic tissues.
3.The protein evolution trees of SLP-2 and TOM40 was constructed,and the transcript factor prediction analysis indicated that the SLP-2 might be regulated by CEBP and ELK1 ect,and the TOM40 might be regulated by the CDPCR3,PAX5 etc.The miRNA prediction presented the miRNA which might regulated the SLP-2 and TOM40,and the prediction 3-D structure of SLP-2 was made,and the antigen epitope of B cell and cytotoxic T lymphatic cell were predicted and presented.
4.The confocal laser scanning microscopy observation of pancreatic immunologic fluorescence cytochemistry indicated that both SLP-2 and TOM40 was expressed in the cytoplasm of pancreatic cancer AsPC-1,BxPC-3 and PANC-1.The PANC-1 cell line had the highest expression level of both SLP-2 and TOM40,and the AsPC-1 cell line had the lowest expression level.
5.The SLP-2 RNA interfering vector pGPU6-GFP-Neo-SLP-2-shRNA was constructed and the pancreatic cell line SW1990 was transfected successful.
CONCLUSIONS
1.SLP-2 and TOM40 were identified as the human pancreatic cancer associated immunogenic membrane antigens.
2.The SLP-2 and TOM40 proteins mainly localized in the cytoplasm of pancreatic cell line AsPC-1,BxPC-3 andPANC-1,the expression of both SLP-2 and TOM40 had significant difference in these three pancreatic cell line,the PANC-1 had the highest expression level but the AsPC-1 had the lowest one.
引文
1.Jemal A,Murray T,Samuels A,Ghafoor A,Ward E,Thun MJ.Cancer statistics,2003.CA Cancer J Clin.2003;53:5-26
2.Surveillance,Epidermiology,and End Results Program,1975-2003,Division of cancer contral and population science,National cancer institute,Bethesda MD 2006
3.Cancer facts&figures 2007,America cancer associtation
4.Moniaux N,Andrianifahanana M,Brand RE,Brtra SK.Multiple roles of mucins in pancreatic cancer,a lethal and challenging malignancy.Br J Cancer 2004;91(9):1633-8
5.Hustinx R PET imaging in assessing gastrointestinal tumors Radiol CLin North Am 2004;42(6):1123-39
6.Bhattacharyya S,Siegel ER,Petersen GM,CHari ST,Suva KL,Haun RS Diagnosis of pancreatic cancer using serum proteomic pfofiling Neoplasia 2004,6(5:674-86)
7.Carr KM,Rosenblatt K,Petersen EF,Liotta LA Genomic and proteomic approaches for studying human cancer prospects for trus patient tailored therapy Hum Genomics,2004;1(2):134-40
8.Koopmann J,Zhang Z,White N,Rosenzweig J,Fedarko NJagannathS,Canto MI,Yeo CJ,Chan DW,GOggins M,Serum diagnosi of pancreatic adenocarcinoma using surface-enhanced laser desorption and ionization mass sepectrometry.Clin Cancer Res 2004;10(3):860-8
9.Bhattacharyya S,siegel ER,Petersen GM,Chari ST,Suva LJ,Haun RS.Diagnosis of pancreatic cancer using serum proteomic profiling,Neoplasia 2004,6(5):674-86
10.Diamandis EP Poing proteomic patterns in biological fluids do they represent the future of cancer diagnosis?Clin Chem 2003;49(8):1272-5
11.Conarads TP,Zhou M,Petricoin EF 3~(rd),Liotta L.Veenstra TD Cancer diagnosis using proteiomic patterns Expert Rev Mol Diagn 2003,3(4):411-20
12.Liotta LA,Ferrari M,Petricoin E Clinical proteomics written in blood Nature2003;425(6961):905
13.Hong SH,Misek DE,Wang H,Puravs E,Giordano TJ,Greenson JK,Brenner DE,Simenone DM,Logsdon CD,Hnash SM,An autoantidoyd mediated immune response to calreticulin isoforms in pancreatic cancer Cancer Res 2004,64(15):5504-10
14.Natkatsura T,Senju S,Yamada K,Gene cloning of immunogenic antigens overexpressed in pancreatic cancer Biophys Res Commun,2001,281(4):936-44.
15.Ning L,Pan B,Zhao YP,Liao Q,Zhang TP,Chen G,Wang WB,Yang YC.,Immunoproteomic screening of human pancreatic cancer associated membrane antigens for early diagnosis,Zhonghua Wai Ke Za Zhi.2007 Jan 1;45(1):34-8
16.《肿瘤免疫学》,杨镇主编,湖北科学技术出版社1998年10月第1版
17.Bence Sipos,Simone Moser,and H.Kalthoff,A comprehensive characterization of pancreatic ductal carcinoma cell lines:towards the establishment of an in vitro research platform.Virchows Arch,2003.442:p.444-52
18.Wang Y,Morrow JS Identification and characterization of human SLP-2,a novel homologue of stomatin(band 7.2b) present in erythrocytes and other tissuesJ Biol Chem.2000 Mar 17;275(11):8062-71
19.Becker L,B.M.,Meisinger C,Hill K,Model K,Krimmer T,Casadio R,Truscott KN,Schulz GE,Pfanner N,Wagner R,Preprotein translocase of the outer mitochondrial membrane:reconstituted Tom40 forms a characteristic TOM pore.J Mol Biol,2005.353(5):p.1011-20
20.Rapaport,D.,How does the TOM complex mediate insertion of precursor proteins into the mitochondrial outer membrane? J Cell Biol,2005.171(3):p.419-23
21.Liyong Zhang,Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma Clin Cancer Res 2006;12(5) March 1,2006,1639-45
22.Wen-feng Cao etc.Prognostic significance of stomatin-like protein 2 overexpression in laryngeal squamous cell carcinoma:clinical,histologic,and immunohistochemistry analyses with tissue microarray
23.张立勇等SLP-2基因在食管鳞癌中的差异表达以及生物信息学分析.世界华人消化杂志.2004,July;12(7):1517-1521
24.冯旺琴等SLP-2 mRNA在子宫内膜癌中的表达及其意义.中华妇产科杂志2005年8月第40卷第8期
1.Liyong Zhang,Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma Clin Cancer Res 2006;12(5) March 1,2006,1639-45
2.Wen-feng Cao etc.Prognostic significance of stomatin-like protein 2 overexpression in laryngeal squamous cell carcinoma:clinical,histologic,and immunohistochemistry analyses with tissue microarray
3.张立勇等 SLP-2 基因在食管鳞癌中的差异表达以及生物信息学分析.世界华人消化杂志.2004,July;12(7):1517-1521
4.冯旺琴等SLP-2 mRNA在子宫内膜癌中的表达及其意义.中华妇产科杂志2005年8月第40卷第8期
5.吴郁,SLP-2基因在宫颈鳞癌中的表达及其功能的初步研究,中国协和医科大学博士学位论文,2006
1.J Kononen,L Bubendorf,A Kallioniemi,et al.Tissue microarrays for high-throughput moleculare pfofiling of tumor specimens.Nat Med,1998,4(7):844-847
2.Liyong Zhang,Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma Clin Cancer Res 2006;12(5) March 1,2006,1639-45
3.Abu-Shakra M,B.D.,Ehrenfeld M,Conrad K,,Cancer ahd autoimmunity:antoimmune and rheumatic features in patients with malignancies.Ann Rheum Dis,2001.60:p.433-41
4.Hong,S.H.,et al.,An autoantibody-mediated immune response to calreticulin isoforms in pancreatic cancer.Cancer Res,2004.64(15):p.5504-10
5.Abu-Shakra M,B.D.,Ehrenfeld M,Conrad K,,Cancer and autoimmunity:antoimmune and rheumatic features in patients with malignancies.Ann Rheum Dis,2001.60:p.433-41
6.Hong,S.H.,et al.,An autoantibody-mediated immune response to calreticulin isoforms in pancreatic cancer.Cancer Res,2004.64(15):p.5504-10
7.Hamanaka Y,Suehiro Y,and Fukui M,Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer.Int J Cancer,2003.103:p.97-100
8.Raedle J,O.G.,Welker M,Roth WK,p53 autoantibodies in patients with pancreatitis and pancreatic carcinoma.Pancreas,1996.13(3):p.241-6
9.Maacke H,H.C.,Miska S,Voss M,,Autoantibodies in sera of pancreatic cancer patients identify recombination factor Rad51 as a tumour-associated antigen.J Cancer Res ClinOncol,2002.128(4):p.219-22
10.Houbiers JG,Nijman HW,van der Burg SH,Drijfhout JW,Kenemans P,van de Velde CJ,Brand A, Momburg F,Kast WM,Melief CJ.In vitro induction of human cytotoxic T lymphocyte responses against peptides of mutant and wild-type p53.Eur J Immunol,1993;23:2072.
11.Gambacorti-Passerini C,Grignani F,Arienti F,Pandolfi PP,Pelicci PG,Parmiani G.Human CD4lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein pml/RAR alpha present in acute promyelocytic leukemia cells.Blood.1993 Mar 1;81(5):1369-75
12.Goodell V,Waisman J,Salazar LG,de la Rosa C,Link J,Coveler AL,Childs JS,Fintak PA,Higgins DM,Disis ML.Level of HER-2/neu protein expression in breast cancer may affect the development of endogenous HER-2/nen-specific immunity.Mol Cancer Ther.2008Mar;7(3):449-54
13.Fukuda M.Possible roles of tumor-associated carbohydrate antigens.Cancer Res,1996;56;2237
14.《肿瘤免疫学》,杨镇主编,湖北科学技术出版社1998年10月第1版
15.《抗体分子与肿瘤》,陈志南刘民陪主编,人民军医出版社2002年6月第一版
16.Rimm DL,Camp RL,Charette LA,et al.Amplication of tissue by construction of tissue microarrays.Exp mol pathol,2001,70(3):255-264
17.BE Marysiak,T Brodzeller,S Buck,et al.Simple,inexpensive method for automating tissue microarray production provides enhanced microarray reproducibility.Appl Immunohitochem Mol Morphol,2003,11(3):269-273
18.Rubin,M.D.,U.Michigan
19.Hoos A,Cordon-Cardo C.Tissue microarray profiling of cancer specimens and cell lines:opportunities and limitations.Lab Invest,2001,81(10):1311-1388
20.Schraml P,Kononen J,Bubendorf L,et al。Tissue microarrays for gene amplicaition surveys in many different tumor types.Clinical cancer research 1999;5(8):1966-75
1.Stamm,S.,et al.,ASD:a bioinformatics resource on alternative splicing.Nucleic Acids Research,2006.34:p.D46-D55
2.Altschul,S.F.,et al.,Gapped BLAST and PSI-BLAST:a new generation of protein database search programs.Nucleic Acids Research,1997.25(17):p.3389-3402
3.Bennett-Lovsey,R.M.,et al.,Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre.Proteins-Structure Function and Bioinformatics,2008.70(3):p.611-625
4.Lambert,C.,et al.,ESyPred3D:Prediction of proteins 3D structures.Bioinformatics,2002.18(9):p.1250-1256.
5.Sayle,R.A.and E.J.Milnerwhite,Rasmol - Biomolecular Graphics for All.Trends in Biochemical Sciences,1995.20(9):p.374-376
6.Ashburner,M.,et al.,Gene Ontology:tool for the unification of biology.Nature Genetics,2000.25(1):p.25-29
7.Jeanmougin,F.,et al.,Multiple sequence alignment with Clustal x.Trends in Biochemical Sciences,1998.23(10):p.403-405
8.Thompson,J.D.,et al.,The CLUSTAL_X windows interface:flexible strategies for multiple sequence alignment aided by quality analysis tools.Nucleic Acids Research,1997.25(24):p.4876-4882
9..Page,R.D.M.,TreeView:An application to display phylogenetic trees on personal computers.Computer Applications in the Biosciences,1996.12(4):p.357-358
10.Wheeler,D.L.,et al.,Database resources of the National Center for Biotechnology.Nucleic Acids Research,2003.31(1):p.28-33
11.Rhodes,D.R.,et al.,Oncomine 3.0:Genes,pathways,and networks in a collection of 18,000cancer gene expression profiles.Neoplasia,2007.9(2):p.166-180
12.Karolchik,D.,et al.,The UCSC Genome Browser Database.Nucleic Acids Research,2003.31(1):p.51-54
13.Karolchik,D.,et al.,The UCSC Genome Browser Database:2008 update.Nucleic Acids Research,2008.36:p.D773-D779.
14.Kent,W.J.,et al.,The human genome browser at UCSC.Genome Research,2002.12(6):p.996-1006.
15.Zeng Y,Wagner EJ,Cullen BR(2002) Both natural and designed micro RNAs can inhibit the expression of cognate mRNA when expressed in human cells.Mol Cell 9:1327-1333
16.Chou PY,Fasman GD.Prediction of the secondary structure of proteins from their amino acid sequence.Adv Enzymol Relat Areas Mol Biol.1978;47:45-148
17.Emini EA,Hughes JV,Perlow DS,Boger J.Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide.J Virol.1985 Sep;55(3):836-9
18.Karplus PA,Schulz GE.Prediction of Chain Flexibility in Proteins - A tool for the Selection of Pcptide Antigens.Naturwissenschafren 1985;72:212-3.
19.Kolaskar AS,Tongaonkar PC.A semi-empirical method for prediction of antigenic determinants on protein antigens.FEBS Lett.1990 Dec 10;276(1-2):172-4
20.Roetzschke O,Falk K,Stevanovic S,et al.Peptide motifs of closely related HLA class Ⅰ molecules encompass substantial differences.Eur J Immunol,1992,22(9):2453-2456
21.HG Rammensee,J Bachmann,NPN Emmerich,OA Bachor and S Stevanovic(1999) SYFPEITHI:database for MHC ligands and peptide motifs.Immunogenetics 50:213-219
22.Rapaport,D.,How does the TOM complex mediate insertion of precursor proteins into the mitochondrial outer membrane? J Cell Biol,2005.171(3):p.419-23
1.Chen WH,Horoszewicz JS,Leong SS,Shimano T,Penetrante R,Sanders WH,Berjian R,Douglass HO,Martin EW,Chu TM(1982) Human pancreatic adenocarcinoma:in vitro and in vivo morphology of a new tumor line established from ascites.In Vitro 18:24-34
2.Lieber M,Mazzetta J,Nelson-Rees W,Kaplan M,Todaro G(1975) Establishment of a continuous tumor-cell line(panc-1)from a human carcinoma of the exocrine pancreas.Int J Cancer 15:741-747
3.Bence Sipos,Simone Moser,and H.Kalthoff,A comprehensive characterization of pancreatic duetal carcinoma cell lines:towards the establishment of an in vitro research platform.Virehows Arch,2003.442:p.444-52
4.Adam D.Humphries,Illo C.Streimann Diana Stojanovski,Amelia J.Johnston Masato Yano Nicholas J.Hoogenraad_+~+,and Michael T.Ryan Dissection of the Mitoehondrial Import and Assembly Pathway for Human Tom40 THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol.280,No.12,Issue of March 25,pp.11535-11543,2005
5.Wang Y,Morrow JS Identification and characterization of human SLP-2,a novel homologue of stomatin(band 7.2b) present in erythrocytes and other tissuesJ Biol Chem.2000 Mar 17;275(11):8062-7
6.Petr Ha jek,Anne Chomyn,and Giuseppe Attardi Identification of a Novel Mitochondrial Complex Containing Mitofusin 2 and Stomatin-like Protein 2 THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL.282,NO.8,pp.5670-5681,February 23,2007
7.Sonnhammer EL,von Heijne G,Krogh A.A hidden Markov model for predicting transmembrane helices in protein sequences Proc Int Conf Intell Syst Mol Biol.1998;6:175-82
8.Small,I.,Peeters,N.,Legeai,F.,Lurin,C.(2004) Predotar:A tool for rapidly screening proteomes for N-terminal targeting sequences.Proteomics,4,1581-1590
1.Fire A,Xu S,Montgomery MK,et al.Potent and specific genetic interference bydouble-stranded RNA in Caenorhabditis elegans.Nature 1998;391(6669):806-811
2.Geley S,M(u|¨)ller C.RNAi:ancient mechanism with a promising future Exp Gerontol 2004;39(7):985-998
3.Iwaki K,Shibata K,Ohta M,Endo Y,Uchida H,Tominaga M,Okunaga R,Kai S,Kitano S.A small interfering RNA targeting proteinase-activated receptor-2 is effective in suppression of tumor growth in a Panel xenograft modal.Int J Cancer.2008 Feb 1;122(3):658-63
4.Liu C,Chen Y,Yu X,Jin C,Xu J,Long J,Ni Q,Fu D,Jin H,Bai C.Proteomic analysis of differential proteins in pancreatic carcinomas:Effects of MBD1 knock-down by stable RNA interference.BMC Cancer.2008 Apr 29;8:121
5.Qiu Z,Huang C,Sun J,Qiu W,Zhang J,Li H,Jiang T,Huang K,Cao J.RNA interference-mediated signal transducers and activators of transcription 3 gene silencing inhibits invasion and metastasis of human pancreatic cancer cells.Cancer Sci.2007 Jul;98(7):1099-106
6.Yu C,Zhang X,Sun G,Guo X,Li H,You Y,Gardner K,Yuan D,Xu Z,DU Q,Dai C,Qian Z,Jiang K,Zhu Y,Jacobs JL,Li QQ,Miao Y.RNA Interference-Mediated Silencing of the Polo-like Kinase 1 Gene Enhances Chemosensitivity to Gemcitabine in Pancreatic Adenocarcinoma Cells J Cell Mol Med.2008 Feb 5
7.Liau SS,Whang E HMGA1 is a molecular determinant of chemoresistance to gemcitabine in pancreatic adenocarcinoma Clin Cancer Res.2008 Mar 1;14(5):1470-7
8.Zhu H,Liang ZY,Ren XY,Liu TH.Small interfering RNAs targeting mutant K-ras inhibit human pancreatic carcinoma cells growth in vitro and in vivo.Cancer Biol Ther.2006 Dec;5(12):1693-8.Epub 2006 Dec 30
9.Liyong Zhang,Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma Clin Cancer Res 2006;12(5) March 1,2006,1639-45
10.冯旺琴等 SLP-2 mRNA在子宫内膜癌中的表达及其意义.中华妇产科杂志2005年8月第40卷第8期
1.Jemal A,Murray T,Samuels A,Ghafoor A,Ward E,Thun MJ.Cancer statistics,2003.CA Cancer J Clin.J Clin.2003;53:5-26.
2.cancer facts&figures 2007 American Caner Society.Atlanta:American cancer society
3.胡家露,努力提高胰腺癌的早期诊断水平,中华内科杂志,1999,38(2):77-78
4.shikawa O,Ohigashi H,Imaoka S,et al.Minute carcinoma of the pancreas measuring 1cm or less in diameter-collective review of Japnese case reports.Hepato-Gastroenterology,1999,46:8-15
5.《胰腺病学》,赵玉沛主编,人民卫生出版社2007年第一版
6.Goggins M.Molecular markers of early pancreatic cancer.J Clin Oncol.2005 Jul 10;23(20):4524-31.Review.
7.Garcea G,Neal CP,Pattenden CJ,Steward WP,Berry DP Molecular prognostic markers in pancreatic cancer:a systematic review Eur J Cancer.2005 Oct;41(15):2213-36.Epub 2005 Sep
8.Su-Hyung Hong,David E.Misek,Hong Wang,Eric Puravs,Thomas J.Giordano,Joel K.Greenson,Dean E.Brenner,Diane M.Simeone,Craig D.Logsdon,and Samir M.HanashlAn Autoantibody-Mediated Immune Response to Calreticulin Isoforms inPancreatic Cancer。 CANCER RESEARCH 64,5504-5510,August 1,2004
9.Hamanaka Y,Suehiro Y,and Fukui M,Circulating anti-MUC1 IgG antibodies avorable prognostic factor for pancreatic cancer.Int J Cancer,2003.103:p.97-100.
10.Raedle J,O.G.,Welker M,Roth WK,p53 autoantibodies in patients with pancreatitis andpancreatic carcinoma.Pancreas,1996.13(3):p.241-6.
11.Maacke H,H.C.,Miska S,Voss M,,Autoantibodies in sera of pancreatic cancer patients identify recombination factor Rad51 as a tumour-associated antigen.J Cancer Res Clin Oncol,2002.128(4):p.219-22.
12.Mugitani H,Furue H,Kako M,Hirota F,Fuse K,Takahashi T,Sakamoto K,Yamada K,Suminaga M,Ezaki M,Judo R.Pancreatic oncofetal antigen(POA) Gan To Kagaku Ryoho.1983Aug;10(8):1737-43.
13.Oguchi H,Homma T,Kawa S,Nagata A,Furuta S,Fukui H.A pancreatic oneofetal antigen (POA):its characterization and application for enzyme immunoassay.Cancer Detect Prev.1984;7(1):51-8。
14.Nishida K,Sugiura M,Yoshikawa T,Kondo M.Enzyme immunoassay of pancreatic oncofetal antigen(POA) as a marker of pancreatic cancer.Gut.1985 May;26(5):450-5
15.Nakaizumi A,Uehara H,Takenaka A,Uedo N,Sakai N,Yano H,Ohigashi H,Ishikawa O,Ishiguro S,Sugano K,Tatsuta M.Diagnosis of pancreatic cancer by cytology and measurement of oncogene and tumor markers in pure pancreatic juice aspirated by endoscopy Hepatogastroenterology.1999 Jan-Feb;46(25):31-7
16.Kikuchi H,Ujiie S,Kanamaru R.Advanced pancreatic cancer successfully treated with continuous infusion of 5-fluorouracil and low-dose cisplatin Intern Med.1998 Jul;37(7):635-7
17.Okusaka T,Okada S,Sato T,Wakasugi H,Saisho H,Furuse J,Ishikawa O,Matsuno S,Yokoyama S.Tumor markers in evaluating the response to radiotherapy in unresectable pancreatic cancer.Hepatogastroenterology.1998 May-Jun;45(21):867-72.
18.Seufferlein T,Adler G(2005) What can be expected from tumor markers in pancreatic cancer.In:Domingnez-Mu(?)oz JE(ed) Clinical pancreatology for practising gastroenterologist andsurgeons.Blackwell,Malden,pp 377-382
19.Sawabu N,Watanabe H,Yamaguchi Y,Ohtsubo K,Motoo Y(2004) Serum tumor markers and molecular biological diagnosisin pancreatic cancer.Pancreas 28:263-267
20.Tempero MA,Uchida E,Takasaki H,Burnett DA,Steplewski Z,Pour PM(1987) Relationship of carbohydrate antigen 19-9 andLewis antigens in pancreatic cancer.Cancer Res 47:5501-5503
21.Koprowski H,Brockhaus M,Blaszczyk M,Magnani J,SteplewskiZ,Ginsburg V(1982) Lewis blood-type may affect the incidence of gastrointestinal cancer.Lancet 1:1332-1333
22.Sperti C,Pasquali C,Catalini S,et al.CA 19-9 as a prognostic index after resection for pancreatic cancer.Oncology,1993,52:137-141.
23.Glenn J,Steinberg W Kurtzman S,et al.Evaluation of the utility of aradioimmunoassay for serum CA 19-9 levels in patients before and after treatment of carcinima of the pancreas.J Clin Oncol,1988,6:462-468
24.Chang JH,Takeuchi T.Clinic significance of meaturement of Span-1 antihen in the diagnosis of pancreatic cancer.J Jpan Pancreas Soc,1990,5:80-88.
25.Steinberg W.The clinical utility of the CA 19-9 tumor-associated antigen Am J Gastroenterol.1990 Apr;85(4):350-5。
26.Sperti C,Pasquali C,Catalini S,Cappellazzo F,Bonadimani B,Behboo R,Pedrazzoli S(1993) CA 19-9 as a prognostic index after resection for pancreatic cancer.J Surg Oncol 52:137-141
27.Lundin J,Roberts PJ,Kuusela P,Haglund C(1994) The prognostic value of preoperative serum levels of CA 19-9 andCEA in patients with pancreatic cancer.Br J Cancer 69:515-519
28.Sperti C,Pasquali C,Catalini S,Cappellazzo F,Bonadimani B,Behboo R,Pedrazzoli S(1993) CA 19-9 as a prognostic indexafter resection for pancreatic cancer.J Surg Oncol 52:137-141
29.Katz A,Hanlon A,Lanciano R,Hoffman J,Coia L(1998) Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy.Int J Radiat Oncol Biol Phys 41:393-396
30.Sperti C,Pasquali C,Catalini S,Cappellazzo F,Bonadimani B,Behboo R,Pedrazzoli S(1993) CA 19-9 as a prognostic indexafter resection for pancreatic cancer.J Surg Oncol 52:137-141
31.Boeck S,Stieber P,Holdenrieder S,Wilkowski R,Heinemann V(2006) Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer.Oncology 70:255-264
32.Cwik G,Wallner G,Skoczylas T,Ciechanski A,Zinkiewicz K(2006) Cancer antigens 19-9 and 125 in the differential diagnosis of pancreatic mass lesions.Arch Surg 141:968-973
33.Liu MP,Guo XZ,Xu JH,Wang D,Li HY,Cui ZM,Zhao JJ,Ren LN(2005) New tumor-associated antigen SC6 in pancreatic cancer.World J Gastroenterol 11:7671-7675
34.Almoguera C,Shibata D,Forrester K,Martin J,Arnheim N,Perucho M(1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.Cell 53:549-554
35.Smit VT,Boot AJ,Smits AM,Fleuren GJ,Cornelisse CJ,Bos JL(1988) KRAS codon 12mutations occur very frequently in pancreatic adenocarcinomas.Nucleic Acids Res 16:7773-7782
36.Berthelemy P,Bouisson M,Escourrou J,Vaysse N,Rumeau JL,Pradayrol L(1995) Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer.Ann Intern Med123:188-191
37.Wenger FA,Zieren J,Peter FJ,Jacobi CA,Muller JM(1999) Kras mutations in tissue and stool samples from atients with pancreatic cancer and chronic pancreatitis.Langenbecks Arch Surg 384:181-186
38.Trumper L,Menges M,Daus H,Kohler D,Reinhard JO,Sackmann M,Moser C,Sek A,Jacobs G,Zeitz M,Pfreundschuh M(2002) Low sensitivity of the ki-ras polymerase chain reaction for diagnosing pancreatic cancer from pancreatic juice and bile:a multicenter prospective trial.J Clin Oncol 20:4331-4337
39.Yamada T,Nakamori S,Ohzato H,Oshima S,Aoki T,Higaki N,Sugimoto K,Akagi K,Fujiwara Y,Nishisho I,Sakon M,Gotoh M,Monden M(1998) Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma:correlation with clinicopathological features.Clin Cancer Res 4:1527-1532
40.Bramhall SR(1998) The use of molecular technology in the differentiation of pancreatic cancer and chronic pancreatitis.Int J Pancreatol 23:83-100
41.Takahashi K,Yamao K,Okubo K,Sawaki A,Mizuno N,Ashida R,Koshikawa T,Ueyama Y,Kasugai K,Hase S,Kakumu S(2005) Differential diagnosis of pancreatic cancer and focal pancreatitis by using EUS-guided FNA.Gastrointest Endosc 61:76-79
42.Arvanitakis M,Van Laethem JL,Parma J,De Maertelaer V,Delhaye M,Deviere J(2004)Predictive factors for pancreatic cancer in patients with chronic pancreatitis in association with Kras gene mutation.Endoscopy 36:535-542
43.Teich N,Mossner J(2004) Molecular analysis of pancreatic juice:a helpful tool to differentiate benign and malignant pancreatic tumors? Dig Dis 22:235-238
44.Boadas J,Mora J,Urgell E,Puig P,Roca M,Cusso X,Capella G,Lluis F,Farre A(2001) Clinical usefulness of K-ras gene mutation detection and cytology in pancreatic juice in the diagnosis and screening of pancreatic cancer.Eur J Gastroenterol Hepatol 13:1153-1159
45.Kim J,Reber HA,Dry SM,Elashoff D,Chen SL,Umetani N,Kitago M,Hines OJ,Kazanjian KK,Hiramatsu S,Bilchik AJ,Yong S,Shoup M,Hoon DS(2006) Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins.Gut 55:1598-1605
46.Schutte M,Hruban RH,Geradts J,Maynard R,Hilgers W,Rabindran SK,Moskaluk CA,Hahn SA,Schwarte-Waldhoff I,Schmiegel W,Baylin SB,Kern SE,Herman JG(1997) Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas.Cancer Res 57:3126-3130
47.Wilentz RE,Geradts J,Maynard R,Offerhaus GJ,Kang M,Goggins M,Yeo CJ,Kern SE,Hruban RH(1998) Inactivation of the p16(INK4A) tumor-suppressor gene in pancreatic duct lesions:loss of intranuclear expression.Cancer Res 58:4740-4744
48.Ohtsubo K, Watanabe H, Yamaguchi Y, Hu YX, Motoo Y, Okai T, Sawabu N (2003) Abnormalities of tumor suppressor gene p16 in pancreatic carcinoma: immunohistochemical and genetic findings compared with clinicopathological parameters. J Gastroenterol 38:663-671
49.Redston MS, Caldas C, Seymour AB, Hruban RH, da Costa L, Yeo CJ, Kern SE (1994) p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. Cancer Res 54:3025-3033
50.Kirsch DG, Kastan MB (1998) Tumor-suppressor p53: implications for tumor development and prognosis. J Clin Oncol 16:3158-3168 Kirsch DG, Kastan MB (1998) Tumor-suppressor p53: implications for tumor development and prognosis. J Clin Oncol 16:3158—3168
51.Casey G, Yamanaka Y, Friess H, Kobrin MS, Lopez ME, Buchler M, Beger HG, Korc M (1993) p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. Cancer Lett 69:151-160
52.Sturm PD, Hruban RH, Ramsoekh TB, Noorduyn LA, Tytgat GN, Gouma DJ, Offerhaus GJ (1998) The potential diagnostic use of K-ras codon 12 and p53 alterations in brush cytology from the pancreatic head region. J Pathol 186:247-253
53.Talar-Wojnarowska R, Malecka-Panas E (2006) Molecular pathogenesis of pancreatic adenocarcinoma: potential clinical implications. Med Sci Monit 12:RA186-RA193
54.Yokoyama M, Yamanaka Y, Friess H, Buchler M, Korc M (1994) p53 expression in human pancreatic cancer correlates with enhanced biological aggressiveness. Anticancer Res 14:2477-2483
55.Costentin L, Pages P, Bouisson M, Berthelemy P, Buscail L, Escourrou J, Pradayrol L, Vaysse N (2002) Frequent deletions of tumor suppressor genes in pure pancreatic juice from patients with tumoral or nontumoral pancreatic diseases. Pancreatology 2:17—25
56.Suehara N, Mizumoto K, Tanaka M, Niiyama H, Yokohata K, Tominaga Y, Shimura H, Muta T, Hamasaki N (1997) Telomerase activity in pancreatic juice differentiates ductal carcinoma from adenoma and pancreatitis. Clin Cancer Res 3:2479-2483
57. Tsutsumi M, Tsujiuchi T, Ishikawa O, Majima T, Yoshimoto M, Sasaki Y, Fukuda T, Oohigashi H, Konishi Y (1997) Increased telomerase activities in human pancreatic duct adenocarcinomas.Jpn J Cancer Res 88:971-976
58.Suehara N, Mizumoto K, Kusumoto M, Niiyama H, Ogawa T,Yamaguchi K, Yokohata K, Tanaka M (1998) Telomerase activity detected in pancreatic juice 19 months before a tumor is detected in a patient with pancreatic cancer. Am J Gastroenterol 93:1967—1971
59.0huchida K, Mizumoto K, Ishikawa N, Sato N, Nagai E, Yamaguchi K, Takaishi H, Ide T, Tanaka M (2004) A highly sensitive and quantitative telomerase activity assay with pancreatic juice is useful for diagnosis of pancreatic carcinoma without problems due to polymerase chain reaction inhibitors: analysis of 100 samples of pancreatic juice from consecutive patients. Cancer 101:2309-2317
60.Seki K, Suda T, Aoyagi Y, Sugawara S, Natsui M, Motoyama H, Shirai Y, Sekine T, Kawai H, Mita Y, Waguri N, Kuroiwa T, Igarashi M, Asakura H (2001) Diagnosis of pancreatic adenocar- Langenbecks Arch Surg
61. Mizumoto K, Tanaka M (2005) Detection of telomerase activity in patients with pancreatic cancer. Methods Mol Med 103:199-205
62. Seki K, Suda T, Aoyagi Y, Sugawara S, Natsui M, Motoyama H, Shirai Y, Sekine T, Kawai H, Mita Y, Waguri N, Kuroiwa T, Igarashi M, Asakura H (2001) Diagnosis of pancreatic adenocar- Langenbecks Arch Surg
63.Ohuchida K, Mizumoto K, Yamada D, Yamaguchi H, Konomi H,Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M (2006)Quantitative analysis of human telomerase reverse transcriptasein pancreatic cancer. Clin Cancer Res 12:2066-2069
64.Yamanaka Y, Friess H, Kobrin MS, Buchler M, Beger HG, Korc M (1993) Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 13:565-569
65.Juhasz M, Nitsche B, Malfertheiner P, Ebert MP (2003) Implications of growth factor alterations in the treatment ofpancreatic cancer. Mol Cancer 2:5
66.Strous GJ, Dekker J (1992) Mucin-type glycoproteins. Crit Rev Biochem Mol Biol 27:57-92
67.Balague C, Gambus G, Carrato C, Porchet N, Aubert JP, Kim YS,Real FX (1994) Altered expression of MUC2, MUC4, and MUC5mucin genes in pancreas tissues and cancer cell lines. Gastroenterology 106:1054-1061
68.Andrianifahanana M, Moniaux N, Schmied BM, Ringel J, Friess H,HollingsworthMA, BuchlerMW, Aubert JP, Batra SK (2001) Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance. Clin Cancer Res 7:4033-4040
69. Koopmann J, Buckhaults P, Brown DA, Zahurak ML, Sato N, Fukushima N, Sokoll LJ, Chan DW, Yeo CJ, Hruban RH, Breit SN, Kinzler KW, Vogelstein B, Goggins M (2004) Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clin Cancer Res 10:2386-2392
70. Koopmann J, Rosenzweig CN, Zhang Z, Canto MI, Brown DA, Hunter M, Yeo C, Chan DW, Breit SN, Goggins M (2006) Serum markers in patients with resectable pancreatic adenocarcinoma: macrophage inhibitory cytokine 1 versus CA19-9. Clin Cancer Res 12:442-446
71.Peng DF, Kanai Y, Sawada M, Ushijima S, Hiraoka N, KitazawaS, Hirohashi S (2006) DNA methylation of multiple tumor-related genes in association with overexpression of DNA methyltransferase 1 (DNMT1) during multistage carcinogenesis of the pancreas. Carcinogenesis 27:1160-1168
72.Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JP, Hruban RH, GogginsM (2000) Hypermethylation of multiple genes in pancreaticadenocarcinoma. Cancer Res 60:1835-1839
73. Hustinx SR, Leoni LM, Yeo CJ, Brown PN, Goggins M, Kern SE,Hruban RH, Maitra A (2005) Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia:evidence of homozygous deletion in a noninvasive precursorlesion. Mod Pathol 18:959-963
74.Fukushima N, Walter KM, Uek T, Sato N, Matsubayashi H, Cameron JL, Hruban RH, Canto M, Yeo CJ, Goggins M (2003) Diagnosing pancreatic cancer using methylation specific PCR analysis of pancreatic juice. Cancer Biol Ther 2:78-83
75.Matsubayashi H, Canto M, Sato N, Klein A, Abe T, Yamashita K,Yeo CJ, Kalloo A, Hruban R, Goggins M (2006) DNA methylation alterations in the pancreatic juice of patients with suspectedpancreatic disease. Cancer Res 66:1208-1217
76.Mazurek S, Boschek CB, Hugo F, Eigenbrodt E (2005) Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 15:300-308
77.Ventrucci M, Cipolla A, Racchini C, Casadei R, Simoni P, Gullo L (2004) Tumor M2-pyruvate kinase, a new metabolic marker for pancreatic cancer. Dig Dis Sci 49:1149-1155
78.Nakae Y, Naruse S, Shibata T, Kitagawa M, Kondo T, Hayakawa T, Kuno N, Kurimoto K. Early detection of pancreatic cancer by serum markers Rinsho Byori. 1994 Feb;42(2): 139-42. Japanese
79.Kotera Y, F.J., Pecher G, Metzgar RS, Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreas, and colon cancer patients. Cancer Res, 1994. 54: p. 2856-60.
80.Gansauge S, G.F., Negri G, Galle P, The role of anti-p53-autoantibodies in pancreatic disorders. Int J Pancreatol, 1996. 19(3): p. 171-8.
81.Imafuku Y, O.G., Hanash S, Proteomics approaches to identify tumor antigen directed antoantibodies as cancer biomarkers. Dis Markers, 2004. 20(3)
2.Surveillance,Epidermiology,and End Results Program,1975-2003,Division of cancer contral and population science,National cancer institute,Bethesda MD 2006
3.Cancer facts&figures 2007,America cancer associtation
4.Moniaux N,Andrianifahanana M,Brand RE,Brtra SK.Multiple roles of mucins in pancreatic cancer,a lethal and challenging malignancy.Br J Cancer 2004;91(9):1633-8
5.Hustinx R PET imaging in assessing gastrointestinal tumors Radiol CLin North Am 2004;42(6):1123-39
6.Bhattacharyya S,Siegel ER,Petersen GM,CHari ST,Suva KL,Haun RS Diagnosis of pancreatic cancer using serum proteomic pfofiling Neoplasia 2004,6(5:674-86)
7.Carr KM,Rosenblatt K,Petersen EF,Liotta LA Genomic and proteomic approaches for studying human cancer prospects for trus patient tailored therapy Hum Genomics,2004;1(2):134-40
8.Koopmann J,Zhang Z,White N,Rosenzweig J,Fedarko NJagannathS,Canto MI,Yeo CJ,Chan DW,GOggins M,Serum diagnosi of pancreatic adenocarcinoma using surface-enhanced laser desorption and ionization mass sepectrometry.Clin Cancer Res 2004;10(3):860-8
9.Bhattacharyya S,siegel ER,Petersen GM,Chari ST,Suva LJ,Haun RS.Diagnosis of pancreatic cancer using serum proteomic profiling,Neoplasia 2004,6(5):674-86
10.Diamandis EP Poing proteomic patterns in biological fluids do they represent the future of cancer diagnosis?Clin Chem 2003;49(8):1272-5
11.Conarads TP,Zhou M,Petricoin EF 3~(rd),Liotta L.Veenstra TD Cancer diagnosis using proteiomic patterns Expert Rev Mol Diagn 2003,3(4):411-20
12.Liotta LA,Ferrari M,Petricoin E Clinical proteomics written in blood Nature2003;425(6961):905
13.Hong SH,Misek DE,Wang H,Puravs E,Giordano TJ,Greenson JK,Brenner DE,Simenone DM,Logsdon CD,Hnash SM,An autoantidoyd mediated immune response to calreticulin isoforms in pancreatic cancer Cancer Res 2004,64(15):5504-10
14.Natkatsura T,Senju S,Yamada K,Gene cloning of immunogenic antigens overexpressed in pancreatic cancer Biophys Res Commun,2001,281(4):936-44.
15.Ning L,Pan B,Zhao YP,Liao Q,Zhang TP,Chen G,Wang WB,Yang YC.,Immunoproteomic screening of human pancreatic cancer associated membrane antigens for early diagnosis,Zhonghua Wai Ke Za Zhi.2007 Jan 1;45(1):34-8
16.《肿瘤免疫学》,杨镇主编,湖北科学技术出版社1998年10月第1版
17.Bence Sipos,Simone Moser,and H.Kalthoff,A comprehensive characterization of pancreatic ductal carcinoma cell lines:towards the establishment of an in vitro research platform.Virchows Arch,2003.442:p.444-52
18.Wang Y,Morrow JS Identification and characterization of human SLP-2,a novel homologue of stomatin(band 7.2b) present in erythrocytes and other tissuesJ Biol Chem.2000 Mar 17;275(11):8062-71
19.Becker L,B.M.,Meisinger C,Hill K,Model K,Krimmer T,Casadio R,Truscott KN,Schulz GE,Pfanner N,Wagner R,Preprotein translocase of the outer mitochondrial membrane:reconstituted Tom40 forms a characteristic TOM pore.J Mol Biol,2005.353(5):p.1011-20
20.Rapaport,D.,How does the TOM complex mediate insertion of precursor proteins into the mitochondrial outer membrane? J Cell Biol,2005.171(3):p.419-23
21.Liyong Zhang,Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma Clin Cancer Res 2006;12(5) March 1,2006,1639-45
22.Wen-feng Cao etc.Prognostic significance of stomatin-like protein 2 overexpression in laryngeal squamous cell carcinoma:clinical,histologic,and immunohistochemistry analyses with tissue microarray
23.张立勇等SLP-2基因在食管鳞癌中的差异表达以及生物信息学分析.世界华人消化杂志.2004,July;12(7):1517-1521
24.冯旺琴等SLP-2 mRNA在子宫内膜癌中的表达及其意义.中华妇产科杂志2005年8月第40卷第8期
1.Liyong Zhang,Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma Clin Cancer Res 2006;12(5) March 1,2006,1639-45
2.Wen-feng Cao etc.Prognostic significance of stomatin-like protein 2 overexpression in laryngeal squamous cell carcinoma:clinical,histologic,and immunohistochemistry analyses with tissue microarray
3.张立勇等 SLP-2 基因在食管鳞癌中的差异表达以及生物信息学分析.世界华人消化杂志.2004,July;12(7):1517-1521
4.冯旺琴等SLP-2 mRNA在子宫内膜癌中的表达及其意义.中华妇产科杂志2005年8月第40卷第8期
5.吴郁,SLP-2基因在宫颈鳞癌中的表达及其功能的初步研究,中国协和医科大学博士学位论文,2006
1.J Kononen,L Bubendorf,A Kallioniemi,et al.Tissue microarrays for high-throughput moleculare pfofiling of tumor specimens.Nat Med,1998,4(7):844-847
2.Liyong Zhang,Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma Clin Cancer Res 2006;12(5) March 1,2006,1639-45
3.Abu-Shakra M,B.D.,Ehrenfeld M,Conrad K,,Cancer ahd autoimmunity:antoimmune and rheumatic features in patients with malignancies.Ann Rheum Dis,2001.60:p.433-41
4.Hong,S.H.,et al.,An autoantibody-mediated immune response to calreticulin isoforms in pancreatic cancer.Cancer Res,2004.64(15):p.5504-10
5.Abu-Shakra M,B.D.,Ehrenfeld M,Conrad K,,Cancer and autoimmunity:antoimmune and rheumatic features in patients with malignancies.Ann Rheum Dis,2001.60:p.433-41
6.Hong,S.H.,et al.,An autoantibody-mediated immune response to calreticulin isoforms in pancreatic cancer.Cancer Res,2004.64(15):p.5504-10
7.Hamanaka Y,Suehiro Y,and Fukui M,Circulating anti-MUC1 IgG antibodies as a favorable prognostic factor for pancreatic cancer.Int J Cancer,2003.103:p.97-100
8.Raedle J,O.G.,Welker M,Roth WK,p53 autoantibodies in patients with pancreatitis and pancreatic carcinoma.Pancreas,1996.13(3):p.241-6
9.Maacke H,H.C.,Miska S,Voss M,,Autoantibodies in sera of pancreatic cancer patients identify recombination factor Rad51 as a tumour-associated antigen.J Cancer Res ClinOncol,2002.128(4):p.219-22
10.Houbiers JG,Nijman HW,van der Burg SH,Drijfhout JW,Kenemans P,van de Velde CJ,Brand A, Momburg F,Kast WM,Melief CJ.In vitro induction of human cytotoxic T lymphocyte responses against peptides of mutant and wild-type p53.Eur J Immunol,1993;23:2072.
11.Gambacorti-Passerini C,Grignani F,Arienti F,Pandolfi PP,Pelicci PG,Parmiani G.Human CD4lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein pml/RAR alpha present in acute promyelocytic leukemia cells.Blood.1993 Mar 1;81(5):1369-75
12.Goodell V,Waisman J,Salazar LG,de la Rosa C,Link J,Coveler AL,Childs JS,Fintak PA,Higgins DM,Disis ML.Level of HER-2/neu protein expression in breast cancer may affect the development of endogenous HER-2/nen-specific immunity.Mol Cancer Ther.2008Mar;7(3):449-54
13.Fukuda M.Possible roles of tumor-associated carbohydrate antigens.Cancer Res,1996;56;2237
14.《肿瘤免疫学》,杨镇主编,湖北科学技术出版社1998年10月第1版
15.《抗体分子与肿瘤》,陈志南刘民陪主编,人民军医出版社2002年6月第一版
16.Rimm DL,Camp RL,Charette LA,et al.Amplication of tissue by construction of tissue microarrays.Exp mol pathol,2001,70(3):255-264
17.BE Marysiak,T Brodzeller,S Buck,et al.Simple,inexpensive method for automating tissue microarray production provides enhanced microarray reproducibility.Appl Immunohitochem Mol Morphol,2003,11(3):269-273
18.Rubin,M.D.,U.Michigan
19.Hoos A,Cordon-Cardo C.Tissue microarray profiling of cancer specimens and cell lines:opportunities and limitations.Lab Invest,2001,81(10):1311-1388
20.Schraml P,Kononen J,Bubendorf L,et al。Tissue microarrays for gene amplicaition surveys in many different tumor types.Clinical cancer research 1999;5(8):1966-75
1.Stamm,S.,et al.,ASD:a bioinformatics resource on alternative splicing.Nucleic Acids Research,2006.34:p.D46-D55
2.Altschul,S.F.,et al.,Gapped BLAST and PSI-BLAST:a new generation of protein database search programs.Nucleic Acids Research,1997.25(17):p.3389-3402
3.Bennett-Lovsey,R.M.,et al.,Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre.Proteins-Structure Function and Bioinformatics,2008.70(3):p.611-625
4.Lambert,C.,et al.,ESyPred3D:Prediction of proteins 3D structures.Bioinformatics,2002.18(9):p.1250-1256.
5.Sayle,R.A.and E.J.Milnerwhite,Rasmol - Biomolecular Graphics for All.Trends in Biochemical Sciences,1995.20(9):p.374-376
6.Ashburner,M.,et al.,Gene Ontology:tool for the unification of biology.Nature Genetics,2000.25(1):p.25-29
7.Jeanmougin,F.,et al.,Multiple sequence alignment with Clustal x.Trends in Biochemical Sciences,1998.23(10):p.403-405
8.Thompson,J.D.,et al.,The CLUSTAL_X windows interface:flexible strategies for multiple sequence alignment aided by quality analysis tools.Nucleic Acids Research,1997.25(24):p.4876-4882
9..Page,R.D.M.,TreeView:An application to display phylogenetic trees on personal computers.Computer Applications in the Biosciences,1996.12(4):p.357-358
10.Wheeler,D.L.,et al.,Database resources of the National Center for Biotechnology.Nucleic Acids Research,2003.31(1):p.28-33
11.Rhodes,D.R.,et al.,Oncomine 3.0:Genes,pathways,and networks in a collection of 18,000cancer gene expression profiles.Neoplasia,2007.9(2):p.166-180
12.Karolchik,D.,et al.,The UCSC Genome Browser Database.Nucleic Acids Research,2003.31(1):p.51-54
13.Karolchik,D.,et al.,The UCSC Genome Browser Database:2008 update.Nucleic Acids Research,2008.36:p.D773-D779.
14.Kent,W.J.,et al.,The human genome browser at UCSC.Genome Research,2002.12(6):p.996-1006.
15.Zeng Y,Wagner EJ,Cullen BR(2002) Both natural and designed micro RNAs can inhibit the expression of cognate mRNA when expressed in human cells.Mol Cell 9:1327-1333
16.Chou PY,Fasman GD.Prediction of the secondary structure of proteins from their amino acid sequence.Adv Enzymol Relat Areas Mol Biol.1978;47:45-148
17.Emini EA,Hughes JV,Perlow DS,Boger J.Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide.J Virol.1985 Sep;55(3):836-9
18.Karplus PA,Schulz GE.Prediction of Chain Flexibility in Proteins - A tool for the Selection of Pcptide Antigens.Naturwissenschafren 1985;72:212-3.
19.Kolaskar AS,Tongaonkar PC.A semi-empirical method for prediction of antigenic determinants on protein antigens.FEBS Lett.1990 Dec 10;276(1-2):172-4
20.Roetzschke O,Falk K,Stevanovic S,et al.Peptide motifs of closely related HLA class Ⅰ molecules encompass substantial differences.Eur J Immunol,1992,22(9):2453-2456
21.HG Rammensee,J Bachmann,NPN Emmerich,OA Bachor and S Stevanovic(1999) SYFPEITHI:database for MHC ligands and peptide motifs.Immunogenetics 50:213-219
22.Rapaport,D.,How does the TOM complex mediate insertion of precursor proteins into the mitochondrial outer membrane? J Cell Biol,2005.171(3):p.419-23
1.Chen WH,Horoszewicz JS,Leong SS,Shimano T,Penetrante R,Sanders WH,Berjian R,Douglass HO,Martin EW,Chu TM(1982) Human pancreatic adenocarcinoma:in vitro and in vivo morphology of a new tumor line established from ascites.In Vitro 18:24-34
2.Lieber M,Mazzetta J,Nelson-Rees W,Kaplan M,Todaro G(1975) Establishment of a continuous tumor-cell line(panc-1)from a human carcinoma of the exocrine pancreas.Int J Cancer 15:741-747
3.Bence Sipos,Simone Moser,and H.Kalthoff,A comprehensive characterization of pancreatic duetal carcinoma cell lines:towards the establishment of an in vitro research platform.Virehows Arch,2003.442:p.444-52
4.Adam D.Humphries,Illo C.Streimann Diana Stojanovski,Amelia J.Johnston Masato Yano Nicholas J.Hoogenraad_+~+,and Michael T.Ryan Dissection of the Mitoehondrial Import and Assembly Pathway for Human Tom40 THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol.280,No.12,Issue of March 25,pp.11535-11543,2005
5.Wang Y,Morrow JS Identification and characterization of human SLP-2,a novel homologue of stomatin(band 7.2b) present in erythrocytes and other tissuesJ Biol Chem.2000 Mar 17;275(11):8062-7
6.Petr Ha jek,Anne Chomyn,and Giuseppe Attardi Identification of a Novel Mitochondrial Complex Containing Mitofusin 2 and Stomatin-like Protein 2 THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL.282,NO.8,pp.5670-5681,February 23,2007
7.Sonnhammer EL,von Heijne G,Krogh A.A hidden Markov model for predicting transmembrane helices in protein sequences Proc Int Conf Intell Syst Mol Biol.1998;6:175-82
8.Small,I.,Peeters,N.,Legeai,F.,Lurin,C.(2004) Predotar:A tool for rapidly screening proteomes for N-terminal targeting sequences.Proteomics,4,1581-1590
1.Fire A,Xu S,Montgomery MK,et al.Potent and specific genetic interference bydouble-stranded RNA in Caenorhabditis elegans.Nature 1998;391(6669):806-811
2.Geley S,M(u|¨)ller C.RNAi:ancient mechanism with a promising future Exp Gerontol 2004;39(7):985-998
3.Iwaki K,Shibata K,Ohta M,Endo Y,Uchida H,Tominaga M,Okunaga R,Kai S,Kitano S.A small interfering RNA targeting proteinase-activated receptor-2 is effective in suppression of tumor growth in a Panel xenograft modal.Int J Cancer.2008 Feb 1;122(3):658-63
4.Liu C,Chen Y,Yu X,Jin C,Xu J,Long J,Ni Q,Fu D,Jin H,Bai C.Proteomic analysis of differential proteins in pancreatic carcinomas:Effects of MBD1 knock-down by stable RNA interference.BMC Cancer.2008 Apr 29;8:121
5.Qiu Z,Huang C,Sun J,Qiu W,Zhang J,Li H,Jiang T,Huang K,Cao J.RNA interference-mediated signal transducers and activators of transcription 3 gene silencing inhibits invasion and metastasis of human pancreatic cancer cells.Cancer Sci.2007 Jul;98(7):1099-106
6.Yu C,Zhang X,Sun G,Guo X,Li H,You Y,Gardner K,Yuan D,Xu Z,DU Q,Dai C,Qian Z,Jiang K,Zhu Y,Jacobs JL,Li QQ,Miao Y.RNA Interference-Mediated Silencing of the Polo-like Kinase 1 Gene Enhances Chemosensitivity to Gemcitabine in Pancreatic Adenocarcinoma Cells J Cell Mol Med.2008 Feb 5
7.Liau SS,Whang E HMGA1 is a molecular determinant of chemoresistance to gemcitabine in pancreatic adenocarcinoma Clin Cancer Res.2008 Mar 1;14(5):1470-7
8.Zhu H,Liang ZY,Ren XY,Liu TH.Small interfering RNAs targeting mutant K-ras inhibit human pancreatic carcinoma cells growth in vitro and in vivo.Cancer Biol Ther.2006 Dec;5(12):1693-8.Epub 2006 Dec 30
9.Liyong Zhang,Stomatin-like protein 2 is overexpressed in cancer and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma Clin Cancer Res 2006;12(5) March 1,2006,1639-45
10.冯旺琴等 SLP-2 mRNA在子宫内膜癌中的表达及其意义.中华妇产科杂志2005年8月第40卷第8期
1.Jemal A,Murray T,Samuels A,Ghafoor A,Ward E,Thun MJ.Cancer statistics,2003.CA Cancer J Clin.J Clin.2003;53:5-26.
2.cancer facts&figures 2007 American Caner Society.Atlanta:American cancer society
3.胡家露,努力提高胰腺癌的早期诊断水平,中华内科杂志,1999,38(2):77-78
4.shikawa O,Ohigashi H,Imaoka S,et al.Minute carcinoma of the pancreas measuring 1cm or less in diameter-collective review of Japnese case reports.Hepato-Gastroenterology,1999,46:8-15
5.《胰腺病学》,赵玉沛主编,人民卫生出版社2007年第一版
6.Goggins M.Molecular markers of early pancreatic cancer.J Clin Oncol.2005 Jul 10;23(20):4524-31.Review.
7.Garcea G,Neal CP,Pattenden CJ,Steward WP,Berry DP Molecular prognostic markers in pancreatic cancer:a systematic review Eur J Cancer.2005 Oct;41(15):2213-36.Epub 2005 Sep
8.Su-Hyung Hong,David E.Misek,Hong Wang,Eric Puravs,Thomas J.Giordano,Joel K.Greenson,Dean E.Brenner,Diane M.Simeone,Craig D.Logsdon,and Samir M.HanashlAn Autoantibody-Mediated Immune Response to Calreticulin Isoforms inPancreatic Cancer。 CANCER RESEARCH 64,5504-5510,August 1,2004
9.Hamanaka Y,Suehiro Y,and Fukui M,Circulating anti-MUC1 IgG antibodies avorable prognostic factor for pancreatic cancer.Int J Cancer,2003.103:p.97-100.
10.Raedle J,O.G.,Welker M,Roth WK,p53 autoantibodies in patients with pancreatitis andpancreatic carcinoma.Pancreas,1996.13(3):p.241-6.
11.Maacke H,H.C.,Miska S,Voss M,,Autoantibodies in sera of pancreatic cancer patients identify recombination factor Rad51 as a tumour-associated antigen.J Cancer Res Clin Oncol,2002.128(4):p.219-22.
12.Mugitani H,Furue H,Kako M,Hirota F,Fuse K,Takahashi T,Sakamoto K,Yamada K,Suminaga M,Ezaki M,Judo R.Pancreatic oncofetal antigen(POA) Gan To Kagaku Ryoho.1983Aug;10(8):1737-43.
13.Oguchi H,Homma T,Kawa S,Nagata A,Furuta S,Fukui H.A pancreatic oneofetal antigen (POA):its characterization and application for enzyme immunoassay.Cancer Detect Prev.1984;7(1):51-8。
14.Nishida K,Sugiura M,Yoshikawa T,Kondo M.Enzyme immunoassay of pancreatic oncofetal antigen(POA) as a marker of pancreatic cancer.Gut.1985 May;26(5):450-5
15.Nakaizumi A,Uehara H,Takenaka A,Uedo N,Sakai N,Yano H,Ohigashi H,Ishikawa O,Ishiguro S,Sugano K,Tatsuta M.Diagnosis of pancreatic cancer by cytology and measurement of oncogene and tumor markers in pure pancreatic juice aspirated by endoscopy Hepatogastroenterology.1999 Jan-Feb;46(25):31-7
16.Kikuchi H,Ujiie S,Kanamaru R.Advanced pancreatic cancer successfully treated with continuous infusion of 5-fluorouracil and low-dose cisplatin Intern Med.1998 Jul;37(7):635-7
17.Okusaka T,Okada S,Sato T,Wakasugi H,Saisho H,Furuse J,Ishikawa O,Matsuno S,Yokoyama S.Tumor markers in evaluating the response to radiotherapy in unresectable pancreatic cancer.Hepatogastroenterology.1998 May-Jun;45(21):867-72.
18.Seufferlein T,Adler G(2005) What can be expected from tumor markers in pancreatic cancer.In:Domingnez-Mu(?)oz JE(ed) Clinical pancreatology for practising gastroenterologist andsurgeons.Blackwell,Malden,pp 377-382
19.Sawabu N,Watanabe H,Yamaguchi Y,Ohtsubo K,Motoo Y(2004) Serum tumor markers and molecular biological diagnosisin pancreatic cancer.Pancreas 28:263-267
20.Tempero MA,Uchida E,Takasaki H,Burnett DA,Steplewski Z,Pour PM(1987) Relationship of carbohydrate antigen 19-9 andLewis antigens in pancreatic cancer.Cancer Res 47:5501-5503
21.Koprowski H,Brockhaus M,Blaszczyk M,Magnani J,SteplewskiZ,Ginsburg V(1982) Lewis blood-type may affect the incidence of gastrointestinal cancer.Lancet 1:1332-1333
22.Sperti C,Pasquali C,Catalini S,et al.CA 19-9 as a prognostic index after resection for pancreatic cancer.Oncology,1993,52:137-141.
23.Glenn J,Steinberg W Kurtzman S,et al.Evaluation of the utility of aradioimmunoassay for serum CA 19-9 levels in patients before and after treatment of carcinima of the pancreas.J Clin Oncol,1988,6:462-468
24.Chang JH,Takeuchi T.Clinic significance of meaturement of Span-1 antihen in the diagnosis of pancreatic cancer.J Jpan Pancreas Soc,1990,5:80-88.
25.Steinberg W.The clinical utility of the CA 19-9 tumor-associated antigen Am J Gastroenterol.1990 Apr;85(4):350-5。
26.Sperti C,Pasquali C,Catalini S,Cappellazzo F,Bonadimani B,Behboo R,Pedrazzoli S(1993) CA 19-9 as a prognostic index after resection for pancreatic cancer.J Surg Oncol 52:137-141
27.Lundin J,Roberts PJ,Kuusela P,Haglund C(1994) The prognostic value of preoperative serum levels of CA 19-9 andCEA in patients with pancreatic cancer.Br J Cancer 69:515-519
28.Sperti C,Pasquali C,Catalini S,Cappellazzo F,Bonadimani B,Behboo R,Pedrazzoli S(1993) CA 19-9 as a prognostic indexafter resection for pancreatic cancer.J Surg Oncol 52:137-141
29.Katz A,Hanlon A,Lanciano R,Hoffman J,Coia L(1998) Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy.Int J Radiat Oncol Biol Phys 41:393-396
30.Sperti C,Pasquali C,Catalini S,Cappellazzo F,Bonadimani B,Behboo R,Pedrazzoli S(1993) CA 19-9 as a prognostic indexafter resection for pancreatic cancer.J Surg Oncol 52:137-141
31.Boeck S,Stieber P,Holdenrieder S,Wilkowski R,Heinemann V(2006) Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer.Oncology 70:255-264
32.Cwik G,Wallner G,Skoczylas T,Ciechanski A,Zinkiewicz K(2006) Cancer antigens 19-9 and 125 in the differential diagnosis of pancreatic mass lesions.Arch Surg 141:968-973
33.Liu MP,Guo XZ,Xu JH,Wang D,Li HY,Cui ZM,Zhao JJ,Ren LN(2005) New tumor-associated antigen SC6 in pancreatic cancer.World J Gastroenterol 11:7671-7675
34.Almoguera C,Shibata D,Forrester K,Martin J,Arnheim N,Perucho M(1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.Cell 53:549-554
35.Smit VT,Boot AJ,Smits AM,Fleuren GJ,Cornelisse CJ,Bos JL(1988) KRAS codon 12mutations occur very frequently in pancreatic adenocarcinomas.Nucleic Acids Res 16:7773-7782
36.Berthelemy P,Bouisson M,Escourrou J,Vaysse N,Rumeau JL,Pradayrol L(1995) Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer.Ann Intern Med123:188-191
37.Wenger FA,Zieren J,Peter FJ,Jacobi CA,Muller JM(1999) Kras mutations in tissue and stool samples from atients with pancreatic cancer and chronic pancreatitis.Langenbecks Arch Surg 384:181-186
38.Trumper L,Menges M,Daus H,Kohler D,Reinhard JO,Sackmann M,Moser C,Sek A,Jacobs G,Zeitz M,Pfreundschuh M(2002) Low sensitivity of the ki-ras polymerase chain reaction for diagnosing pancreatic cancer from pancreatic juice and bile:a multicenter prospective trial.J Clin Oncol 20:4331-4337
39.Yamada T,Nakamori S,Ohzato H,Oshima S,Aoki T,Higaki N,Sugimoto K,Akagi K,Fujiwara Y,Nishisho I,Sakon M,Gotoh M,Monden M(1998) Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma:correlation with clinicopathological features.Clin Cancer Res 4:1527-1532
40.Bramhall SR(1998) The use of molecular technology in the differentiation of pancreatic cancer and chronic pancreatitis.Int J Pancreatol 23:83-100
41.Takahashi K,Yamao K,Okubo K,Sawaki A,Mizuno N,Ashida R,Koshikawa T,Ueyama Y,Kasugai K,Hase S,Kakumu S(2005) Differential diagnosis of pancreatic cancer and focal pancreatitis by using EUS-guided FNA.Gastrointest Endosc 61:76-79
42.Arvanitakis M,Van Laethem JL,Parma J,De Maertelaer V,Delhaye M,Deviere J(2004)Predictive factors for pancreatic cancer in patients with chronic pancreatitis in association with Kras gene mutation.Endoscopy 36:535-542
43.Teich N,Mossner J(2004) Molecular analysis of pancreatic juice:a helpful tool to differentiate benign and malignant pancreatic tumors? Dig Dis 22:235-238
44.Boadas J,Mora J,Urgell E,Puig P,Roca M,Cusso X,Capella G,Lluis F,Farre A(2001) Clinical usefulness of K-ras gene mutation detection and cytology in pancreatic juice in the diagnosis and screening of pancreatic cancer.Eur J Gastroenterol Hepatol 13:1153-1159
45.Kim J,Reber HA,Dry SM,Elashoff D,Chen SL,Umetani N,Kitago M,Hines OJ,Kazanjian KK,Hiramatsu S,Bilchik AJ,Yong S,Shoup M,Hoon DS(2006) Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins.Gut 55:1598-1605
46.Schutte M,Hruban RH,Geradts J,Maynard R,Hilgers W,Rabindran SK,Moskaluk CA,Hahn SA,Schwarte-Waldhoff I,Schmiegel W,Baylin SB,Kern SE,Herman JG(1997) Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas.Cancer Res 57:3126-3130
47.Wilentz RE,Geradts J,Maynard R,Offerhaus GJ,Kang M,Goggins M,Yeo CJ,Kern SE,Hruban RH(1998) Inactivation of the p16(INK4A) tumor-suppressor gene in pancreatic duct lesions:loss of intranuclear expression.Cancer Res 58:4740-4744
48.Ohtsubo K, Watanabe H, Yamaguchi Y, Hu YX, Motoo Y, Okai T, Sawabu N (2003) Abnormalities of tumor suppressor gene p16 in pancreatic carcinoma: immunohistochemical and genetic findings compared with clinicopathological parameters. J Gastroenterol 38:663-671
49.Redston MS, Caldas C, Seymour AB, Hruban RH, da Costa L, Yeo CJ, Kern SE (1994) p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions. Cancer Res 54:3025-3033
50.Kirsch DG, Kastan MB (1998) Tumor-suppressor p53: implications for tumor development and prognosis. J Clin Oncol 16:3158-3168 Kirsch DG, Kastan MB (1998) Tumor-suppressor p53: implications for tumor development and prognosis. J Clin Oncol 16:3158—3168
51.Casey G, Yamanaka Y, Friess H, Kobrin MS, Lopez ME, Buchler M, Beger HG, Korc M (1993) p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. Cancer Lett 69:151-160
52.Sturm PD, Hruban RH, Ramsoekh TB, Noorduyn LA, Tytgat GN, Gouma DJ, Offerhaus GJ (1998) The potential diagnostic use of K-ras codon 12 and p53 alterations in brush cytology from the pancreatic head region. J Pathol 186:247-253
53.Talar-Wojnarowska R, Malecka-Panas E (2006) Molecular pathogenesis of pancreatic adenocarcinoma: potential clinical implications. Med Sci Monit 12:RA186-RA193
54.Yokoyama M, Yamanaka Y, Friess H, Buchler M, Korc M (1994) p53 expression in human pancreatic cancer correlates with enhanced biological aggressiveness. Anticancer Res 14:2477-2483
55.Costentin L, Pages P, Bouisson M, Berthelemy P, Buscail L, Escourrou J, Pradayrol L, Vaysse N (2002) Frequent deletions of tumor suppressor genes in pure pancreatic juice from patients with tumoral or nontumoral pancreatic diseases. Pancreatology 2:17—25
56.Suehara N, Mizumoto K, Tanaka M, Niiyama H, Yokohata K, Tominaga Y, Shimura H, Muta T, Hamasaki N (1997) Telomerase activity in pancreatic juice differentiates ductal carcinoma from adenoma and pancreatitis. Clin Cancer Res 3:2479-2483
57. Tsutsumi M, Tsujiuchi T, Ishikawa O, Majima T, Yoshimoto M, Sasaki Y, Fukuda T, Oohigashi H, Konishi Y (1997) Increased telomerase activities in human pancreatic duct adenocarcinomas.Jpn J Cancer Res 88:971-976
58.Suehara N, Mizumoto K, Kusumoto M, Niiyama H, Ogawa T,Yamaguchi K, Yokohata K, Tanaka M (1998) Telomerase activity detected in pancreatic juice 19 months before a tumor is detected in a patient with pancreatic cancer. Am J Gastroenterol 93:1967—1971
59.0huchida K, Mizumoto K, Ishikawa N, Sato N, Nagai E, Yamaguchi K, Takaishi H, Ide T, Tanaka M (2004) A highly sensitive and quantitative telomerase activity assay with pancreatic juice is useful for diagnosis of pancreatic carcinoma without problems due to polymerase chain reaction inhibitors: analysis of 100 samples of pancreatic juice from consecutive patients. Cancer 101:2309-2317
60.Seki K, Suda T, Aoyagi Y, Sugawara S, Natsui M, Motoyama H, Shirai Y, Sekine T, Kawai H, Mita Y, Waguri N, Kuroiwa T, Igarashi M, Asakura H (2001) Diagnosis of pancreatic adenocar- Langenbecks Arch Surg
61. Mizumoto K, Tanaka M (2005) Detection of telomerase activity in patients with pancreatic cancer. Methods Mol Med 103:199-205
62. Seki K, Suda T, Aoyagi Y, Sugawara S, Natsui M, Motoyama H, Shirai Y, Sekine T, Kawai H, Mita Y, Waguri N, Kuroiwa T, Igarashi M, Asakura H (2001) Diagnosis of pancreatic adenocar- Langenbecks Arch Surg
63.Ohuchida K, Mizumoto K, Yamada D, Yamaguchi H, Konomi H,Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M (2006)Quantitative analysis of human telomerase reverse transcriptasein pancreatic cancer. Clin Cancer Res 12:2066-2069
64.Yamanaka Y, Friess H, Kobrin MS, Buchler M, Beger HG, Korc M (1993) Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 13:565-569
65.Juhasz M, Nitsche B, Malfertheiner P, Ebert MP (2003) Implications of growth factor alterations in the treatment ofpancreatic cancer. Mol Cancer 2:5
66.Strous GJ, Dekker J (1992) Mucin-type glycoproteins. Crit Rev Biochem Mol Biol 27:57-92
67.Balague C, Gambus G, Carrato C, Porchet N, Aubert JP, Kim YS,Real FX (1994) Altered expression of MUC2, MUC4, and MUC5mucin genes in pancreas tissues and cancer cell lines. Gastroenterology 106:1054-1061
68.Andrianifahanana M, Moniaux N, Schmied BM, Ringel J, Friess H,HollingsworthMA, BuchlerMW, Aubert JP, Batra SK (2001) Mucin (MUC) gene expression in human pancreatic adenocarcinoma and chronic pancreatitis: a potential role of MUC4 as a tumor marker of diagnostic significance. Clin Cancer Res 7:4033-4040
69. Koopmann J, Buckhaults P, Brown DA, Zahurak ML, Sato N, Fukushima N, Sokoll LJ, Chan DW, Yeo CJ, Hruban RH, Breit SN, Kinzler KW, Vogelstein B, Goggins M (2004) Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clin Cancer Res 10:2386-2392
70. Koopmann J, Rosenzweig CN, Zhang Z, Canto MI, Brown DA, Hunter M, Yeo C, Chan DW, Breit SN, Goggins M (2006) Serum markers in patients with resectable pancreatic adenocarcinoma: macrophage inhibitory cytokine 1 versus CA19-9. Clin Cancer Res 12:442-446
71.Peng DF, Kanai Y, Sawada M, Ushijima S, Hiraoka N, KitazawaS, Hirohashi S (2006) DNA methylation of multiple tumor-related genes in association with overexpression of DNA methyltransferase 1 (DNMT1) during multistage carcinogenesis of the pancreas. Carcinogenesis 27:1160-1168
72.Ueki T, Toyota M, Sohn T, Yeo CJ, Issa JP, Hruban RH, GogginsM (2000) Hypermethylation of multiple genes in pancreaticadenocarcinoma. Cancer Res 60:1835-1839
73. Hustinx SR, Leoni LM, Yeo CJ, Brown PN, Goggins M, Kern SE,Hruban RH, Maitra A (2005) Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia:evidence of homozygous deletion in a noninvasive precursorlesion. Mod Pathol 18:959-963
74.Fukushima N, Walter KM, Uek T, Sato N, Matsubayashi H, Cameron JL, Hruban RH, Canto M, Yeo CJ, Goggins M (2003) Diagnosing pancreatic cancer using methylation specific PCR analysis of pancreatic juice. Cancer Biol Ther 2:78-83
75.Matsubayashi H, Canto M, Sato N, Klein A, Abe T, Yamashita K,Yeo CJ, Kalloo A, Hruban R, Goggins M (2006) DNA methylation alterations in the pancreatic juice of patients with suspectedpancreatic disease. Cancer Res 66:1208-1217
76.Mazurek S, Boschek CB, Hugo F, Eigenbrodt E (2005) Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 15:300-308
77.Ventrucci M, Cipolla A, Racchini C, Casadei R, Simoni P, Gullo L (2004) Tumor M2-pyruvate kinase, a new metabolic marker for pancreatic cancer. Dig Dis Sci 49:1149-1155
78.Nakae Y, Naruse S, Shibata T, Kitagawa M, Kondo T, Hayakawa T, Kuno N, Kurimoto K. Early detection of pancreatic cancer by serum markers Rinsho Byori. 1994 Feb;42(2): 139-42. Japanese
79.Kotera Y, F.J., Pecher G, Metzgar RS, Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreas, and colon cancer patients. Cancer Res, 1994. 54: p. 2856-60.
80.Gansauge S, G.F., Negri G, Galle P, The role of anti-p53-autoantibodies in pancreatic disorders. Int J Pancreatol, 1996. 19(3): p. 171-8.
81.Imafuku Y, O.G., Hanash S, Proteomics approaches to identify tumor antigen directed antoantibodies as cancer biomarkers. Dis Markers, 2004. 20(3)