Dukes B期大肠癌蛋白质组学研究
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摘要
大肠癌在不同地区、种族、年龄发病率不同。在西方国家发病率居第二位,并且发病率和死亡率均有逐年上升的趋势。大肠癌发病的年龄趋向老年化,根据收集分析我国20世纪70年代文献报告,我国大肠癌患者的中位年龄在45岁左右,比欧洲的报告提前12-18年。我国70年代文献中40岁以下大肠癌病人一般占35%左右,30岁以下病人占12%左右。而近5年的数据表明大肠癌中位发病年龄为57岁左右。大肠癌发病中位年龄后移,发病进一步向高年龄组集中。因此,高年龄组无疑是大肠癌发病的高危人群。老年人大肠癌如今已经成为国际上医学研究的热点之一。很有必要对其发病、转移、复发机制进行研究。
传统上,国内外学者对大肠癌研究主要集中在:①流行病学调查,前瞻性;②回顾性比较研究;③尸体解剖分析。随着科学进步,对大肠癌研究的方法愈来愈多,层面越来越高。如组织化学染色、PCR方法、蛋白水平研究等等。近年蛋白质水平研究的迅猛发展,为大肠癌的研究提供了又一新的方法。本实验通过双向凝胶电泳与质谱技术和二维液质联用技术及免疫印迹技术,鉴定出临床病理分期中大肠癌DukesB期肿瘤和癌旁组织的差异蛋白,为大肠癌临床诊断及发病机制的研究寻找蛋白标志物;并可进一步为大肠癌的早期诊断、生物学治疗等寻找新的靶点。
实验结果:应用双向凝胶电泳与质谱技术实验最后得到大肠癌和癌旁组织差异蛋白21个,其中有14个肿瘤组织蛋白质表达上调,7个肿瘤组织蛋白质表达下调。应用二维液质联用技术分析最后得到大肠癌和癌旁组织差异蛋白44个,其中有21个肿瘤组织蛋白质表达上调,23个肿瘤组织蛋白质表达下调。两种技术路线所得实验结果中共有13个蛋白得到一致的鉴定结果,其中:在肿瘤组织中表达上调的有7个蛋白质,如Hemoglobin Lepore-Baltimore,60 kDa heat shock protein,ATP synthase subunit alpha,Keratin type I cytoskeletal 18,Protein disulfide-isomerase A3,Alpha-enolase,Isoform 1 of Nucleophosmin;在肿瘤组织中表达下调的有6个蛋白质,如Isoform 1 of Desmuslin,Transgelin,Desmin,Calponin-1,Heat shock protein beta-1,Isoform 2 of Vinculin。
The Colorectal cancer is one of current global most common mali-gnant tumors, its incidence rate and the mortality rate is increasing year by year. The Colorectal cancer tended to shift and recur easily, and has become the5th in mortality rate of maligrant tumor in our country, it is quite necessary to conduct the research of its morbidity, the shift and the recrudescence mechanism .
Traditionally, the domestic and foreign scholars,researches of colorectal cancer mainly focus on :①Epidemiology investigation, foresightedness;②Foresighted and retrospective comparative studies③autopsy analysis. Nowadays, along with scientific progress, the methods for the study of colon cancer are increasing rapidly, and the studying fields are more and more broad. Such as histochemistry dyes, PCR method, protein studies and so on. Particularly in recent years, the research in Protein levels developed more quickly,and the study on colorectal cancer has steped into a new world.
With the human genome project's implementation and advancement,life science research has entered the post-genome era. In this era, the main studying object of life science is functional genomics, including structural genomics and proteomics research.Although there are many species' genome has been sequenced, but more than half of gene's function is unknown in these genomes . Currently, the strategies of the functional genomics uses, such as gene chip, serial analysis of gene expression (SAGE), which are considered in the context of mRNA from the cells , and its premise is that the level of mRNA of cells can reflect the protein expression levels. But this is not entirely the case, in the mRNA point of view, actually, it only includes the level of transcription regulation, and can not fully represent the level of protein expression. Protein's complex post-translational modification, protein's sub-cellular localization or migration, and protein-protein interactions is almost impossible to judge from the mRNA level.Needless to say, protein is executor of physiological functions, is the direct embodiment of the phenomenon of life, and the study of protein structure and function will directly clarify the conditions of life under physiological or pathological changes in the mechanism. The existence forms and activity patterns of the protein itself, such as post-translational modification, protein-protein interactions and protein conformation and so on, still depends on the direct study of proteins to resolve. Although the protein's special nature, such as variability, diversity and so on, has led to the result that the research techniques of protein are far more complex and difficult than nucleic acid technology , but it is these characteristics affect the entire life course.
The traditional study approach of a single protein has been unable to meet the requirements of post-genome era, it is because [2]:①Biological phenomena's occurrence is often multi-factors,it will inevitably involve multiple proteins;②the involvement of multiple proteins is interwoven into a network, or parallel to occur, or showed a cascade relationship;③In the implementation of physiological functions, the performance of proteins are diverse, dynamic, it is not as basically fixed as the genome. Therefore,if one need to have a comprehensive and in-depth understanding of the complexity of life, it is essential to study protein on a overall, dynamic, network level. Thus, in 1994, Australia's Macquarie University, Wilkins and Williams first proposed proteome concept, which originated from the heterozygosity of two words,protein and genome , which is defined as: all types of proteins expressed by a cell in a particular physiological or pathological state. Proteomics which takes all proteins expressed by the genome, namely protein group,as studying object, is a new area of research. Proteomics is divided into two types: 1、expressional proteomics which is to study the change of quantity of protein expression between different samples .2、functional proteomics which establish cell signal transduction pathway network through the separation of protein complexes and the systematic study protein-protein interactions . Proteomics has a rich studying content ,a great many technology platform and more and more advanced technological means. In that case, rational selection of clinical specimens, is the key to the expressional proteomics studies.
Generally, International organizations still follow the Dukes improved TNM staging and the staging method proposed by UICC. According to the Dukes law's supplementin our country , divides into: Cancers limited in the intestinal wall is within the DukesA period. Serosal invasion through the intestinal wall and / or serosa things, but no lymph node metastasis is the B phase. With lymph node metastasis belongs to the C phase, in which lymph node metastasis is limited to the vicinity, such as colon wall and lymph nodes are for the C1 period; if transferred to the Department of Film and mesangial root node is the C2 period. Already have distant metastasis or peritoneal metastasis or extensive invasion to adjacent organs and can not be removed is the D period
Based on the above principle, this experiment identified stages of clinical pathology, the Patient tumor organization of Colorectal cancer in Dukes B period and different proteins of adjacent tissues in the pathological classification through the proteomic approach.,it can provide protein markers for the pathological classification of colorectal cancer ;it can be further used to find new targets for early diagnosis and biology treatment of colorectal cancer .
Under the application of two-dimensional gel electrophoresis and mass spectrometry experiments , we finally obtained organization different proteins of tumors and adjacent tissues 21, including 14 up- regulated proteins and 7 protein down. With the application of two-dimensional LC-MS analysis, we could obtain 44 organization different proteins of cancer and adjacent tissues, including 21 up- regulated proteins and 23 protein down. From the two technical route we find 13 proteins to obtain the consistent appraisal result, and including 7 up- regulated proteins ,for example, Hemoglobin Lepore-Baltimore, 60 kDa heat shock protein, ATP synthase subunit alpha , Keratin type I cytoskeletal 18 , Protein disulfide-isomerase A3,Alpha-enolase,Isoform 1 of Nucleophosmin;and 6 protein down, for example, Isoform 1 of Desmuslin,Transgelin,Desmin,Calponin-1,Heat shock protein beta-1,Isoform 2 of Vinculin.
In order to confirm the accuracy of our experiment,we selected two protein(Enolase,Hemogobin) among the 21different proteins of cancer and adjacent tissues by Dimensional gel electrophoresis and mass spectrometry experiments respectively and verified the accuracy of two-dimensional gel electrophoresis by immunity signature experiment; in the same way , we also selected two protein(Vinculin,Talin)among 44 different proteins which were finally received from tumor and adjacentissues in the two-dimensional liquid chromatography analysis and verified the accuracy of Two-dimensional LC-MS experiment by immunity signature experiment. In addition ,we discussed the four proteins above ,which further illustrates their meaning in the incidence of disease ,colorectal cancer diagnosis or treatment and other aspects.
传统上,国内外学者对大肠癌研究主要集中在:①流行病学调查,前瞻性;②回顾性比较研究;③尸体解剖分析。随着科学进步,对大肠癌研究的方法愈来愈多,层面越来越高。如组织化学染色、PCR方法、蛋白水平研究等等。近年蛋白质水平研究的迅猛发展,为大肠癌的研究提供了又一新的方法。本实验通过双向凝胶电泳与质谱技术和二维液质联用技术及免疫印迹技术,鉴定出临床病理分期中大肠癌DukesB期肿瘤和癌旁组织的差异蛋白,为大肠癌临床诊断及发病机制的研究寻找蛋白标志物;并可进一步为大肠癌的早期诊断、生物学治疗等寻找新的靶点。
实验结果:应用双向凝胶电泳与质谱技术实验最后得到大肠癌和癌旁组织差异蛋白21个,其中有14个肿瘤组织蛋白质表达上调,7个肿瘤组织蛋白质表达下调。应用二维液质联用技术分析最后得到大肠癌和癌旁组织差异蛋白44个,其中有21个肿瘤组织蛋白质表达上调,23个肿瘤组织蛋白质表达下调。两种技术路线所得实验结果中共有13个蛋白得到一致的鉴定结果,其中:在肿瘤组织中表达上调的有7个蛋白质,如Hemoglobin Lepore-Baltimore,60 kDa heat shock protein,ATP synthase subunit alpha,Keratin type I cytoskeletal 18,Protein disulfide-isomerase A3,Alpha-enolase,Isoform 1 of Nucleophosmin;在肿瘤组织中表达下调的有6个蛋白质,如Isoform 1 of Desmuslin,Transgelin,Desmin,Calponin-1,Heat shock protein beta-1,Isoform 2 of Vinculin。
The Colorectal cancer is one of current global most common mali-gnant tumors, its incidence rate and the mortality rate is increasing year by year. The Colorectal cancer tended to shift and recur easily, and has become the5th in mortality rate of maligrant tumor in our country, it is quite necessary to conduct the research of its morbidity, the shift and the recrudescence mechanism .
Traditionally, the domestic and foreign scholars,researches of colorectal cancer mainly focus on :①Epidemiology investigation, foresightedness;②Foresighted and retrospective comparative studies③autopsy analysis. Nowadays, along with scientific progress, the methods for the study of colon cancer are increasing rapidly, and the studying fields are more and more broad. Such as histochemistry dyes, PCR method, protein studies and so on. Particularly in recent years, the research in Protein levels developed more quickly,and the study on colorectal cancer has steped into a new world.
With the human genome project's implementation and advancement,life science research has entered the post-genome era. In this era, the main studying object of life science is functional genomics, including structural genomics and proteomics research.Although there are many species' genome has been sequenced, but more than half of gene's function is unknown in these genomes . Currently, the strategies of the functional genomics uses, such as gene chip, serial analysis of gene expression (SAGE), which are considered in the context of mRNA from the cells , and its premise is that the level of mRNA of cells can reflect the protein expression levels. But this is not entirely the case, in the mRNA point of view, actually, it only includes the level of transcription regulation, and can not fully represent the level of protein expression. Protein's complex post-translational modification, protein's sub-cellular localization or migration, and protein-protein interactions is almost impossible to judge from the mRNA level.Needless to say, protein is executor of physiological functions, is the direct embodiment of the phenomenon of life, and the study of protein structure and function will directly clarify the conditions of life under physiological or pathological changes in the mechanism. The existence forms and activity patterns of the protein itself, such as post-translational modification, protein-protein interactions and protein conformation and so on, still depends on the direct study of proteins to resolve. Although the protein's special nature, such as variability, diversity and so on, has led to the result that the research techniques of protein are far more complex and difficult than nucleic acid technology , but it is these characteristics affect the entire life course.
The traditional study approach of a single protein has been unable to meet the requirements of post-genome era, it is because [2]:①Biological phenomena's occurrence is often multi-factors,it will inevitably involve multiple proteins;②the involvement of multiple proteins is interwoven into a network, or parallel to occur, or showed a cascade relationship;③In the implementation of physiological functions, the performance of proteins are diverse, dynamic, it is not as basically fixed as the genome. Therefore,if one need to have a comprehensive and in-depth understanding of the complexity of life, it is essential to study protein on a overall, dynamic, network level. Thus, in 1994, Australia's Macquarie University, Wilkins and Williams first proposed proteome concept, which originated from the heterozygosity of two words,protein and genome , which is defined as: all types of proteins expressed by a cell in a particular physiological or pathological state. Proteomics which takes all proteins expressed by the genome, namely protein group,as studying object, is a new area of research. Proteomics is divided into two types: 1、expressional proteomics which is to study the change of quantity of protein expression between different samples .2、functional proteomics which establish cell signal transduction pathway network through the separation of protein complexes and the systematic study protein-protein interactions . Proteomics has a rich studying content ,a great many technology platform and more and more advanced technological means. In that case, rational selection of clinical specimens, is the key to the expressional proteomics studies.
Generally, International organizations still follow the Dukes improved TNM staging and the staging method proposed by UICC. According to the Dukes law's supplementin our country , divides into: Cancers limited in the intestinal wall is within the DukesA period. Serosal invasion through the intestinal wall and / or serosa things, but no lymph node metastasis is the B phase. With lymph node metastasis belongs to the C phase, in which lymph node metastasis is limited to the vicinity, such as colon wall and lymph nodes are for the C1 period; if transferred to the Department of Film and mesangial root node is the C2 period. Already have distant metastasis or peritoneal metastasis or extensive invasion to adjacent organs and can not be removed is the D period
Based on the above principle, this experiment identified stages of clinical pathology, the Patient tumor organization of Colorectal cancer in Dukes B period and different proteins of adjacent tissues in the pathological classification through the proteomic approach.,it can provide protein markers for the pathological classification of colorectal cancer ;it can be further used to find new targets for early diagnosis and biology treatment of colorectal cancer .
Under the application of two-dimensional gel electrophoresis and mass spectrometry experiments , we finally obtained organization different proteins of tumors and adjacent tissues 21, including 14 up- regulated proteins and 7 protein down. With the application of two-dimensional LC-MS analysis, we could obtain 44 organization different proteins of cancer and adjacent tissues, including 21 up- regulated proteins and 23 protein down. From the two technical route we find 13 proteins to obtain the consistent appraisal result, and including 7 up- regulated proteins ,for example, Hemoglobin Lepore-Baltimore, 60 kDa heat shock protein, ATP synthase subunit alpha , Keratin type I cytoskeletal 18 , Protein disulfide-isomerase A3,Alpha-enolase,Isoform 1 of Nucleophosmin;and 6 protein down, for example, Isoform 1 of Desmuslin,Transgelin,Desmin,Calponin-1,Heat shock protein beta-1,Isoform 2 of Vinculin.
In order to confirm the accuracy of our experiment,we selected two protein(Enolase,Hemogobin) among the 21different proteins of cancer and adjacent tissues by Dimensional gel electrophoresis and mass spectrometry experiments respectively and verified the accuracy of two-dimensional gel electrophoresis by immunity signature experiment; in the same way , we also selected two protein(Vinculin,Talin)among 44 different proteins which were finally received from tumor and adjacentissues in the two-dimensional liquid chromatography analysis and verified the accuracy of Two-dimensional LC-MS experiment by immunity signature experiment. In addition ,we discussed the four proteins above ,which further illustrates their meaning in the incidence of disease ,colorectal cancer diagnosis or treatment and other aspects.
引文
[1] Xing B, ThuppalS, JedsadayanmataA, et a.l TA205, an anti-talin monoclonal antibody, inhibits integrin-talin interaction[ J]. FEBS Lett, 2006, 580(8): 2027-2032.
[2] Parkin DM,Pisani P,Ferlay J.Global cancer statistics[J]. CA Cancer J Clin,1999, 49(1):33-64.
[3]赖跃兴.靖大道.大肠癌流行因素的研究现状[J].中国肿瘤.2007.5:323-326.
[4]徐富星.等.大肠癌研究现状[J] .国际消化病杂志.2006.12:36-37
[5] Izard T, Evans G, Borgon RA, et a.l Vinculin activation by talin through helical bundle conversion[J]. Nature, 2004, 427(6970): 171-175.
[6] Bakin AV, SafinaA, RinehartC, et a.l A critical role of tropomyosins in TGF - beta regulation of the actin cy-toskeleton and cellmotility in epithelial cells[J]. MolBi-olCel,l 2004, 15(10): 4682-4694.
[7] Vogelste in B Fearon ER.. A genetic model for colorectal tumori genesis [J]. Cell 1990 61(5):759-767.
[8] Bois PR, OH' ara BP, Nietlispach D, et a.l The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin[J]. J BiolChem, 2006, 281(11): 7228-7236.
[9] GiannoneG, JiangG, Sutton DH, et a.l Talin1 is critical for force-dependent reinforcement of initial integrin-cytoskeleton bonds butnot tyrosine kinase activation [J]. J Cell Bio,l 2003, 163(2): 409-419.
[10] Zhao ZS, Manser E, Loo TH, Lim L. Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly. Mol Cell Biol 2000; 20: 6354-6363
[11] Lakka SS, Bhattacharya A, Mohanam S, Boyd D, Rao JS. Regulation of the uPA gene in various grades of human glioma cells. Int J Oncol 2001; 18: 71-79
[12] Raval G N, Bharadwaj S,Levine E A, et al.Loss of expression of tropomyosin-1,a novel classⅡtumor suppressor that induces anoikis,in primary breast tumors. Oncogene,2003,22(40):6194-6203.
[13] KremesrkohtenJ,PlaasC, ndler5etal.SynaPotdin,amoleeulein- volvedin the ofmrationofhte dendrities PineaPpaaruts,15adualaeti al-pha一actin in binding Portein. JNeuorehem.2005Feb;92(3):597一606.
[14] SENG UPTA P K, S M ITH EM, KI M K, et al . DNA hyper methyla2 tion near the transcrip tion start site of collagen al pha2 ( I ) gene oc2 curs in both cancer cell lines and p rimary colorectal cancers[ J ].Cancer Res, 2003, 63 (8) : 17892 1797.
[15] Yeo M, Kim DK, Park HJ,et al. Loss of transgelin in repeated bouts of ulcerative colitis-induced colon carcinogenesis. Proteomics. 2006; 6(4): 1158-1165.
[16] Kaiser BK, Yim D, Chow IT, et al. Disulphide-isomerase-enabled shedding of tumour-associated NKG2D ligands. Nature. 2007; 447(7143):482-486.
[17] Talieri M, Papadopoulou S, Scorilas A, et al. Cathepsin B and Cathepsin D expression in the progression of colorectal adenoma to carcinoma. Cancer Letters 2004 205 97-106.
[18] Goldstein N S. Armin M. Bojarowski T. Epidermal growth factor receptor immunohistochemical reactivity in patients with Amerrican Joint Committee on Cancer StageⅣcolon adenocarcinoma:implieations for a standardized scoring system[J].Cancer 2001.92:[33].
[19] Craig L.Jordan D B. The epidermal growth factor as a targer for colorectoal cancer therapy [J]. Seminoncol. 2005.32:52
[20] Zosia Chustecka. Sunitinib and Sorafenib Confirm Efficacy in Renal Cell Carcinoma [J]. N Engl J Med. 2007.356:115.
[21] Haynes PA ,Gygi SP ,Fig D , et al . Proteome analysis : biological assay or data achieve ? [J ] . Electrophoresis ,1998 ,19 (12) :1862-1871.
[22] Rappsilber J, Mann M. What does it mean to identify a protein in proteomics? Trends Biochem Sci 2002;27:74-78
[23] Chambers G,Lawrie L,Cash P,Murray GI. Proteomics: a new approach to the study of disease. J Pathol 2000;192:280-288
[24] Banks RE, Dunn MJ, Hochstrasser DF, Sanchez JC, Blackstock W, Pappin DJ, Selby PJ. Proteomics: new perspectives,
[25]王凤茹.电泳应注意的几个关键问题[J].生物技术通报2005,6,62-64
[26]熊兴东,刘新光,李恩民.双向电泳技术及其在肿瘤研究中的应用[J].MODERN ONCOLOGY,2005,113(12):270-272.
[27]朱玉光李玮.磁性高分子微球的制备及其在生物医学上的应用[J].胶体与聚合物2006,24(4)43-45.
[28]李洪利.亲和层析技术在现代蛋白质研究中的应用及新发展.海洋湖沼通报.2005,2:87-89.
[29]杨芄原,钱小红.生物质谱技术与方法[M].科学出版社1999,1-100.
[30] Howard W,John C,Pau1.Neoplasms of the stomach,Cancer Medicine,E5th[J].American Cancer Society,2001,1355.
[31] Merchant M,Weinberger SR.Recent advancements in surface-enhanced laser desorption ionization-time of flight。mass spectrometry[J].Electrophoresis,2000,21:1164 -1177.
[32] Issaq HJ,VeenstraTD,ConradsTP,et al,The SELDI TOFMS approach to proteomics:protein profiling and biomarker identification[J].Biochem Biophys Res Commun,2002,292:587-592.
[33] Vihinen M. Bioinformatics in proteomics. Biomol Eng 2001;18:241-248.
[34] Fenyo D.Identifying the proteome:software tools. Curr Opin Biotechnol 2000;11:391-395.
[35] Wojcik J, Schachter V. Proteomic databases and software on the web. Brief Bioin 2000;1:250-259
[36] Mann M, Pandey A. Use of mass spectrometry-derived data to annotate nucleotide and protein sequence databases. Trends Biochem Sci 2001;26:54-61.
[37] Shevchenko A, Sunyaev S, Loboda A, Shevchenko A, Bork P, Ens W, Standing KG. Charting the proteomes of organisms with unsequenced genomes by MALDI-quadrupole time-of-flight mass spectrometry and BLAST homology searching. Anal Chem 2001;73:1917-1926.
[38] Maggio ET,Ramnarayan K. Recent developments in computational proteomics. Trends Biotechnol 2001;19:266-272.
[39] Frankfurt, Olga ; Licht,Jonathan D ; Tallman, MartinSetal. Molecular characterization of acute myeloid leukemia and its impacton treatment[J]. Leukemia, 2007,29(6):635–649
[40] Kuendgen A,Stupp C,Aivado M,et al.Treatment of myelodys-plastic syndromeswith valproic acid alone or in combination with all-trans retinoic acid.Blood, 2004,104:1266-1269
[41] Witzig TE.Kaulmann SH.Inhibition of the phosphatidylinositol 3-kinase/ mammalian arget of rapamycin pathway in hematologic malignancies.Curr Treat Options Oncol.2006.7(4):285-294.
[42] Alaiya AA ,Franzen B ,Auer G, et al . Cancer proteomics :from identifi2 cation of novel markers to creation of artifical leaning models for tumor classification[J ] . Electrophoresis ,2000 ,21 (11) :1210-1217.
[43] Conroy SE ,Sasieni PD ,Amin V , et al . Antibodies to heat shock protein 27areassociated with improves survival inpatients with breast cancer [J ] .Br J Cancer ,1998 ,77 (19) :1875-1879.
[44] STONE RM,DEANGELO D J,KLIMEK V,et al Acute myeloid leukemiapatients with an activating mutation in FLT3 respond to a small molecule FLT3 tyrosine kinase inhibitor,PKC412[J].Blood,2005,105(1):54-60.。
[45] DeAngeloDJ,AmreinPC,KovacsovicsT,etal.Phase1/2studyof tandutinib(MLN518) plus standard induction chemotherapy innewly diagnosed acute myelogenous leukemia(AML)[abstract].Blood2006;108:617.
[46] Recher O.Beyne-RauzyO,DemurC,et al.Antileukemic activityof rapamycin in acute myeloid leukemia.Blood。2005.105(6):2527-2534.
[47] COHENL S ,ES COBARP F ,SC HARM C,etal .Three dimensional power Doppler ultrasound imporves the diagnostic accuracy for ovarian cancer prediction[ j].G ynecol Oncol,2001,82:40一48.
[48] 1 PETRICOINEF ,AR DEKANIAM ,HITTBA ,et al .Use of porteomic pattems in serum to identify ovarian cancer[ J1.L ancet, 2002 ,359:572一577.
[49] Picaluda P P,Martinei IT G,RondonunM,et al.Gemtuzumab ozogamicin for relapsed and refractory acute myeloid leukemia and myeloid sarcomas[J].Leuk Lymphoma,2004,45(9):1791-1795
[50] Sarto C,Frutiger S,Cappellano F,Sanchez JC,Doro G,Catanzaro F,Hughes GJ,Hochstrasser DF,Mocarelli P. Modified expression of plasma glutathione peroxidase and manganese superoxidise dismutase in human renal cell carcinoma. Electrophoresis 1999;20:3458-3466.
[51] Menendez V ,Fernandez2Suarez A ,Galan JA ,et al . Diagnosis of bladdercancer by analysis of urinary fibronectin [J ] . U2rology ,2005 ,65 (2) :2842289
[52] Law RH, Zhang Q, McGowan S, Buckle AM, Silverman GA, Wong W et al. An overview of the serpin superfamily. Genome Biol 2006; 7: 216.
[53] Lindblad D, Blomenkamp K, Teckman J. Alpha-1-antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model. Hepatology 2007; 46:1228–1235.
[54] Wirth PJ ,Hoang TN ,Benjamin T.Micropreparative immobilized Phgra2 dient two dimensional electrophoresis in combination with protein mi2 crosequenxcing for the analysis of human liver proeins [J]. Electro2 phoresis, 1995 ,16 (11) :1946-1960.
[55] Seow TK,Ong SE ,Liang RC , et al . Two dimensional electrophoresis map of the human hepato cellular carcinoma cell line , HCC M, and identification of the separated proteins by mass spectrometry[J ] . Elec2 trophoresis ,2000 ,21 (9) :1787-1813.
[56]俞利荣,王楠,吴高德,等.人肝癌细胞系BEL7404和正常肝细胞系L 02表达的蛋白质组双向凝胶电泳分析[J ] .科学通报,2000 ,45 (3) :170-178.
[57] Chaurand P , DaGue BB , Pearsall RS , et al. Profiling proteins from azoxymethane induced color tumors at the molecular level by matrix as 2 sisted laser desorpionP ionization mass spectrometry [ J ] . Proteomics ,2001 ,1 (10) :1320-1326.
[58] Bargagna-Mohan P, Ravindranath PP, Mohan R. Small molecule anti-angiogenic probes of the ubiquitin proteasome pathway: potential application to choroidal neovascularization. Invest Ophthalmol Vis Sci 2006; 47:4138-45.
[59] Seliger B, Fedorushchenko A, Brenner W, Ackermann A, Atkins D, Hanash S, Lichtenfels R. Ubiquitin COOH-terminal hydro-lase 1: a biomarker of renal cell carcinoma associated with en-hanced tumor cell proliferation and migration. Clin Cancer Res2007; 13:27-37.
[60] Chen YR, Juan HF, Huang HC, Huang HH, Lee YJ, Liao MY,Tseng CW, Lin LL, Chen JY, Wang MJ, Chen JH, Chen YJ.Quantitative proteomic and genomic profiling reveals metasta-sis-related protein expression patterns in gastric cancer cells. JProteome Res 2006; 5:2727-42.
[61] Okuzawa K,Franzen B ,LindholmJ , et al . Characterization of gene ex2pression in clinical lung cancer materials by two dimensional polylam2 idegel electrophoresis[J ] . Electrophoresis ,1994 ,15 (324) :382-390.
[62] Sarto C ,Marocchi A ,Sarto C , et al . Renal cell carcinoma and normal kidney protein expression[J ] . Electrophoresis ,1997 ,18 (34) :599-604.
[63] Kawauchi T, Chihama K, Nabeshima Y, Hoshino M. The in vivo roles of STEF/Tiam1, Rac1 and JNK in cortical neuronal migration. EMBO J 2003; 22: 4190-4201
[64] Lakka SS, Bhattacharya A, Mohanam S, Boyd D, Rao JS. Regulation of the uPA gene in various grades of human glioma cells. Int J Oncol 2001; 18: 71-79
[65] KeimD ,Hailat N ,Melhem R , et al . Proliferatin related expression of p19P nm23 nucleosidediphophate kinase [ J ] . J Clin Invest , 1992 , 89(6) :919-924.
[66] Ostergaard M,Rasmussen HH ,Nielsen HV , et al . Proteome profiling ofbladder squamous cell carcinomas :identification of markers that define their degree of differentiantion [J ] . Cancer Res ,1997 ,57 (20) :4111-4117.
[67] Huang J ,Hu N ,Taylor P , et al . An approach to Proteomic analysis of human tumors[J ] .Mol Carcinog ,2000 ,27 (3) :158-165.
[68] Lin JD ,Chan EC ,Weng HF , et al . Two dimensional electorophoretic analysis of membranous protein from human thyroid tissues and cancer cell lines[J ] . Electrophoresis ,1998 ,19 (18) :3213-3216.
[69] Rasmussen RK,Ji Hong ,Eddes JS , et al. Two dimensional gel database of human breast carcinoma cell expressed proteins :Anupdate[J].Elec2 trophoresis,1998 ,19 (5) :818-828.
[70] Miller A ,Mukhtar O ,Aaluri SR , et al . Two2and three2dimensional TEE differentiation of lymphoma involving the atrial septum from lipomatous hypertrophy[J]. Echocardiography ,2001 ,18 (3) :205-209.
[71]许洋.蛋白质指纹图谱技术在实验诊断与I临床医学中的研究进展.基础医学与临床.2007,27(2):334-340.
[72] Zhao L, Liu L, Wang S, et a.l Differential proteomic a-nalysis ofhuman colorectal carcinoma cell linesmetastasis-associated proteins[ J]. J Cancer Res Clin Onco,l 2007, 133(10): 771-782.
[73] RavalGN, Bharadwaj S, Levine EA, et a.l Loss of ex-pression of tropomyosin-1, a novel classⅡtumor sup-pressor that induces anoikis, in primary breast tumors[J]. Oncogene, 2003, 22(40): 6194-6203.
[74] Posadas EM, Simpkins F, Liotta LA, et a.l Proteomic a-nalysis for the early detection and rational treatment of cancer-realistic hope? [J]. Ann Onco,l 2005, 16(1):16-22.
[75] Bellacosa A. Genetic hits and mutation rate in colorectal tumorigenesis: versatility ofKnudson s theory and implica-tions for cancerprevention[J]. GenesChromosomes Canc-er, 2003, 38(4): 382-388.
[76] PolleyAC, Mulholland F, Pin C, et a.l Proteomic analy-sis reveals field-wide changes in protein expression in themorphologically normalmucosa of patients with colorectalneoplasia[J]. CancerRes, 2006, 66(13): 6553-6562.
[77] JEMAL A, MURRAY T, WARD E, et al . Cancer statistics[ J ].CA Cancer J Clin, 2005, 55 (1) : 102 30.
[78] SH I YY, WANG HC, YI N YH, et al . I dentification and analysis of tumour2 ass ociated antigens in hepat ocellular carcinoma [ J ]. B rJ Cancer, 2005, 92 (5) : 9292 934.
[79] Talieri M, Papadopoulou S, Scorilas A, et al. Cathepsin B and Cathepsin D expression in the progression of colorectal adenoma to carcinoma. Cancer Letters 2004 205 97-106.
[80] Subramanian A,Miller D M. Structural analysis of alpha-enolase.Mapp ing the functional domains involved in down-regulation of the c-myc p rotooncogene [ J ]. J Biol Chem, 2000, 275 ( 8 ) : 5958-5965.
[81] Fougerousse F, Edom-Vovard F,Merkulova T, et al. The muscle-specific enolase is an early marker of human myogenesis [ J ]. J Muscle Res CellMotil, 2001, 22 (6) : 534-544.
[82] KellerA, Rouzeau J D, Farhadian F, et al. Differential exp ression ofα- andβ-enolase genes during rat heart development and hypertrophy[ J ]. Am J Physiol, 1995, 269 (6Pt2) : H1843-H1851.
[83] Kang HJ, Jung SK, Kim SJ, et al. Structure of human alpha-enolase ( hENO1) , a multifunctional glycolytic enzyme [ J ]. Acta Crystallogr D Biol Crystallogr, 2008, 64 (6) : 651-657.
[84] [TerrierB, Degand N, Guilpain P, et al. Alpha2enolase: a target of anti-bodies in infectious and autoimmune diseases [ J ]. Autoimmun Rev,2007, 6 (3) : 176-182.
[85] KellerA, Peltzer J, Carpentier G, et al. Interactions of enolase isoforms withtubulin and microtubules duringmyogenesis [ J ]. Biochim Biophys Acta, 2007, 1770 (6) : 919-926.
[86] Perconti G, Ferro A, Amato F, et al. The Kelch protein NS1-BP interacts with alpha-enolase /MBP-1 and is involved in c-myc gene transcriptional control [ J ]. Biochim Biophys Acta, 2007, 1773 ( 12 ) :1774-1785.
[87] Sousa LP, BrasilBS, Silva BM, et al. Characterization of alpha-enolase as an interferon-alpha - alpha 1 regulated gene [ J ]. FrontBiosci, 2005,10: 2534-2547.
[88] Jorgensen L G,Osterlind K, Genolla J ,et al. Serum neuron-specific enolase (S-NSE) and the prognosis in smallcell lung cancer (SCLC) :a combined multivariable analysis on data from nine centres. Br J Cancer ,1996 ,74 :463-467.
[89] Kinloch A, TatzerV,Wait R, et al. Identification of citrullinated alpha-enolase as a candidate autoantigen in rheumatoid arthritis[ J ].Arthritis Res Ther, 2005, 7 (6) : R1421-1429.
[90] Ren G, Adamus G. Cellular targets of anti-alpha-enolase autoanti-bodies of patientswith autoimmune retinopathy[ J ]. J Autoimmun,2004, 23 (2) : 161-167.
[91] Nahm D H, Lee K H, Shim J Y. Identification of alpha-enolase as an autoantigen associated with severe asthma [ J ]. J Allergy Clin Immunol, 2006, 118 (2) : 376-381.
[92] Takashima M, Kuramitsu Y, Yokoyama Y, et al. Overexp ression of alpha enolase in hepatitis C virus-related hepatocellular carcinoma: association with tumor p rogression as determined by p roteomic analysis[ J ]. Proteomics, 2005, 5 (6) : 1686-1692.
[93] Chang G C,Liu K J, Hsieh C L, et al. Identification of alpha-enolase as an autoantigen in lung cancer: its overexp ression is associated with clinical outcomes[ J ]. Clin Cancer Res, 2006, 12 ( 19) :5746-5754.
[94] Roozendaal C, ZhaoMH, Horst G, et al. Catalase andα-enolase: two novel granulocyte autoantigens in inflammatory bowel disease ( IBD ) [ J ]. Clin Exp Immunol, 1998, 112 (1) : 10-16.
[95] Vermeulen N, Arijs I, Joossens S, et al. Anti-α-enolase antibodies in patientswith inflammatory bowel disease [ J ]. Clin Chem, 2008, 54(3) : 534-541 .
[96] Durany N, Joseph J, Campo E, et al. Phosphoglycerate mutase, 2, 3 bisphospho-glycerate Phosphatase, creation kinase and enolase activity and isoenzymes iin lung, colon and liver carcinomas [ J ]. Br J Cancer,1997, 76 (9) : 1139-1149
[97] Stieruma R, GaspariM, Dommels Y, et al. Proteome analysis reveals novel p roteins associated with p roliferation and differentiation of the colorectal cancer cell line Caco-2 [ J ]. Biochim Biophys Acta, 2003,1650 (1-2) : 73-91.
[98] KatayamaM, Nakano H, Ishiuchi A, et al. Protein pattern difference in the colon cancer Protein pattern difference in the colon cancer cell lines examined by two-dimensional differential in-gel electrophoresis and mass spectrometry [ J ]. Surg Today, 2006, 36 (12) : 1085-1093.
[99] WangLH, Fang XC, Pan GZ. Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis [ J ]. Gut, 2004, 53(8) : 1096-1101.
[100] Bassotti G, VillanacciV, Cathomas G, et al. Enteric neuropathology of the terminal ileum in patients with intractable slow-transit constipation[ J ]. Hum Pathol, 2006, 37 (10) : 1252-1258.
[101]韩金凤,王芳癌性贫血的研究进展辽宁中医药大学学报2009, 1 1 (10): 118-119
[102]沈文香,陈敏斌,沈刚,周丽娜重组人促红细胞生成素治疗肿瘤化疗中贫血的临床研究,南京医科大学学报(自然科学版)2008 ,28 (8 ):1054- 1056
[103]曹传武,徐家华,徐霁充,张家兴,王杰军回顾方法分析大肠癌的部位、分期、营养状况、治疗方法、性别、年龄等因素与贫血的相关性。同济大学学报(医学版) 2009,30(1 ):52-55
[104]房朝辉,李魁秀,宋藏珠,牛书怀,王争国探讨Ⅱ、Ⅲ期宫颈癌患者血红蛋白水平与放射治疗近期、远期疗效的关系河北医科大学学报2004 ,25 (4 ):200-201
[105]秦瑞,吴达荣,胡俊,毕向军研究对晚期癌性贫血患者血清促红细胞生成素( EPO)的水平及其对患者贫血症状作用的临床意义。临床和实验医学杂志2006,5(2)107-108
[106] Kuroda N ,Narase , Miyazaki E , et al . Vinculin : its possible use asmarker ofnormal collecting ducts and renal neoplasms with collecting duct system phenotype[J ] .Mod Pathol ,2000 ,13 (10) :1109 - 1114.
[107] MacDonald N, Shivers W, Narum D,et al. Endostatin binds tropomyosin. A potential modulator of the antitumor activity of endostatin [J]. J Biol Chem,2001,276(27):25190-25196.
[108] Sibley K, Cuthbert-Heavens D, Knowles MA. Loss of heterozy- gosityat4p16.3and mutation of FGFR3in transitional cell car-cinoma [J]. Oncogene,2001,20:686-691.
[109] Vokes EE, Crawford J, Bogart J, et al . Concurrent chemoradi o2 therapy for unresectable stageⅢnon2small cell lung cancer[ J ].Clin Cancer Res, 2005, 11 (2) : 5045 - 5050.
[110] Bois PR, OπHara BP, Nietlis pach D, et al . The vinculin bindingsites of talin and alpha2 actinin are sufficient t o activate vinculin [ J ]. J Biol Chem, 2006, 281 (11) : 7228 - 7236.
[111] I zard T, Evans G, Borgon RA, et al . Vinculin activation by talinthr ough helical bundle conversion [ J ]. Nature, 2004, 427(6970) : 171 - 175.
[112] Kelly DF, Taylor DW, Bakolitsa C, et al . Structure of the alpha2 actinin2 vinculin head domain comp lex determined by cryo2 elec2tron micr oscopy[ J ]. J Mol Biol, 2006, 357 (2) : 562 - 573.
[113] Roberts GC, Critchley DR. Structural and bi ophysical p roperties of the integrin2 ass ociated cyt oskeletal p r otein talin [ J ]. Biophys Rev, 2009, 1 (2) : 61 - 69.
[114] Xing B, Thuppals, Jedsadayanmata A, et al . TA205, an anti2talin monocl onal antibody, inhibits integrin2talin interacti on [ J ]. FEBSLett, 2006, 580 (8) : 2027 - 2032.
[115] Monkley SJ, Zhou XH, Kinst on SJ, et al . Disrup ti on of the talin gene arrestsmouse development at the gastrulati on stage[ J ]. DevDyn, 2000, 219 (4) : 560 - 574.
[116] RobertsGC, Critchley DR. Structural and biophysical properties of the integrin-associated cytoskeletal protein talin[ J]. Biophys Rev, 2009, 1(2): 61-69.
[117] ]Xing B, Thuppals, Jedsadayanmata A, et a.l TA205, an anti-talin monoclonal antibody, inhibits integrin-talin interaction[J]. FEBS Lett, 2006, 580(8):2027-2032.
[118] Monkley SJ, Zhou XH,Kinston SJ, et a.l Disruption of the talin gene arrestsmouse developmentat the gastrulation stage[J]. DevDyn, 2000, 219(4): 560-574.
[119]杨红军,丁彦青,周军.大肠癌组织中talin mRNA的表达及意义[J].山东医药, 2008, 48(3): 1-2.
[120] Humphries JD, Wang P, Streuli C, et a.l Vinculin controls focal adhesion formation by direct interactionswith talin and actin[J]. JCellBio,l 2007, 179(5): 1043-1057.
[121] Vokes EE, Crawford J, Bogart J, et a.l Concurrent chemoradio-therapy for unresectable stageⅢnon-small cell lung cancer[J].Clin CancerRes, 2005, 11(2): 5045-5050.
[122] BoisPR, O Hara BP, Nietlispach D, et a.l The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin [J]. J BiolChem, 2006, 281(11): 7228-7236.
[123] Izard T, EvansG, Borgon RA, et a.l Vinculin activation by talin through helical bundle conversion [ J]. Nature, 2004, 427(6970): 171-175.
[124] Kelly DF, TaylorDW, Bakolitsa C, et a.l Structure of the alpha-actinin-vinculin head domain complex determined by cryo-elec- tronmicroscopy[J]. JMolBio,l 2006, 357(2): 562-573.
[125] Garcia-Alvarez B, de Pereda JM,Calderwood DA, et a.l Struc-tural determinants of integrin recognition by talin[J].MolCel,l2003, 11(1): 49~58.
[126] LingK,Doughman RL,FirestoneAJ, et a.l Type I gamma phos-phatidylinositol phosphate kinase targets and regulates focal ad-hesions[J].Nature, 2002, 420(6911): 89~93.
[127] DiPaoloG,PellegriniL,Letinic K, et a.l Recruitment and regu-lation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin[J].Nature,2002,420(6911):85~9.
[128] LingK,Doughman RL, IyerVV, et a.l Tyrosine phosphorylation of type Igamma phosphatidylinositol phosphate kinase by Srcregulates an integrin-talin switch[ J]. J Cell Bio,l 2003, 163(6): 1339~49.
[129] Tadokork S, ShattilSJ,EtoK, eta.l Talin binding to integrin be-ta tails: a final common step in integrin activation[J]. Science,2003, 302(5642): 103~6.
[130] Barsukov IL, PrescotA,BateN, eta.l Phosphatidylinositolphos-phate kinase typel gamma and betal- integrin cytoplasmic do-main bind to the same region in the talin FERM domain[ J]. JBiolChem, 2003, 278(33): 31202~9.
[131] Hynes RO. Integrins: bidirectiona,l allosteric signalingmachines [J].Cel,l 2002, 110(6): 673~87.
[132] Woodside DG, Liu S, Ginsberg MH. Integrin activation [ J]·ThrombHaemost, 2001, 86(1): 316~23.
[133] Hughes PE,Diaz-GonzalezF,LeongL, eta.l Breaking the in-tegrin hinge. A defined structural constraint regulates integrinsignaling[J]. J BiolChem, 1996, 271(12): 6571~4.
[134]刘勇,顾康生Talin、vinculin在食管癌中的表达及其临床意义临床肿瘤学杂志2009,14(9):787-790
[135] RobertsGC, Critchley DR. Structural and biophysical properties of the integrin-associated cytoskeletal protein talin[ J]. Biophys Rev, 2009, 1(2): 61-69.
[136] Xing B, Thuppals, Jedsadayanmata A, et a.l TA205, an anti-talin monoclonal antibody, inhibits integrin-talin interaction[J]. FEBS Lett, 2006, 580(8): 2027-203
[137] Humphries JD, Wang P, Streuli C, et a.l Vinculin controls focal adhesion formation by direct interactionswith talin and actin[J]. JCellBio,l 2007, 179(5): 1043-1057.
[138] Vokes EE, Crawford J, Bogart J, et a.l Concurrent chemoradio-therapy for unresectable stageⅢnon-small cell lung cancer[J]. Clin CancerRes, 2005, 11(2): 5045-5050.
[139] BoisPR, O Hara BP, Nietlispach D, et a.l The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin [J]. J BiolChem, 2006, 281(11): 7228-7236.
[140] Xing B, Thuppal S, Jedsadayanmata A, et al. TA205, an anti -talin monoclonal antibody, inhibits integrin - talin interaction [J]. FEBS Lett, 2006, 580(8):2027~ 2032
[141] Kelly DF, TaylorDW, Bakolitsa C, et a.l Structure of the alpha-actinin-vinculin head domain complex determined by cryo-elec- tronmicroscopy[J]. JMolBio,l 2006, 357(2): 562-573.
[2] Parkin DM,Pisani P,Ferlay J.Global cancer statistics[J]. CA Cancer J Clin,1999, 49(1):33-64.
[3]赖跃兴.靖大道.大肠癌流行因素的研究现状[J].中国肿瘤.2007.5:323-326.
[4]徐富星.等.大肠癌研究现状[J] .国际消化病杂志.2006.12:36-37
[5] Izard T, Evans G, Borgon RA, et a.l Vinculin activation by talin through helical bundle conversion[J]. Nature, 2004, 427(6970): 171-175.
[6] Bakin AV, SafinaA, RinehartC, et a.l A critical role of tropomyosins in TGF - beta regulation of the actin cy-toskeleton and cellmotility in epithelial cells[J]. MolBi-olCel,l 2004, 15(10): 4682-4694.
[7] Vogelste in B Fearon ER.. A genetic model for colorectal tumori genesis [J]. Cell 1990 61(5):759-767.
[8] Bois PR, OH' ara BP, Nietlispach D, et a.l The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin[J]. J BiolChem, 2006, 281(11): 7228-7236.
[9] GiannoneG, JiangG, Sutton DH, et a.l Talin1 is critical for force-dependent reinforcement of initial integrin-cytoskeleton bonds butnot tyrosine kinase activation [J]. J Cell Bio,l 2003, 163(2): 409-419.
[10] Zhao ZS, Manser E, Loo TH, Lim L. Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly. Mol Cell Biol 2000; 20: 6354-6363
[11] Lakka SS, Bhattacharya A, Mohanam S, Boyd D, Rao JS. Regulation of the uPA gene in various grades of human glioma cells. Int J Oncol 2001; 18: 71-79
[12] Raval G N, Bharadwaj S,Levine E A, et al.Loss of expression of tropomyosin-1,a novel classⅡtumor suppressor that induces anoikis,in primary breast tumors. Oncogene,2003,22(40):6194-6203.
[13] KremesrkohtenJ,PlaasC, ndler5etal.SynaPotdin,amoleeulein- volvedin the ofmrationofhte dendrities PineaPpaaruts,15adualaeti al-pha一actin in binding Portein. JNeuorehem.2005Feb;92(3):597一606.
[14] SENG UPTA P K, S M ITH EM, KI M K, et al . DNA hyper methyla2 tion near the transcrip tion start site of collagen al pha2 ( I ) gene oc2 curs in both cancer cell lines and p rimary colorectal cancers[ J ].Cancer Res, 2003, 63 (8) : 17892 1797.
[15] Yeo M, Kim DK, Park HJ,et al. Loss of transgelin in repeated bouts of ulcerative colitis-induced colon carcinogenesis. Proteomics. 2006; 6(4): 1158-1165.
[16] Kaiser BK, Yim D, Chow IT, et al. Disulphide-isomerase-enabled shedding of tumour-associated NKG2D ligands. Nature. 2007; 447(7143):482-486.
[17] Talieri M, Papadopoulou S, Scorilas A, et al. Cathepsin B and Cathepsin D expression in the progression of colorectal adenoma to carcinoma. Cancer Letters 2004 205 97-106.
[18] Goldstein N S. Armin M. Bojarowski T. Epidermal growth factor receptor immunohistochemical reactivity in patients with Amerrican Joint Committee on Cancer StageⅣcolon adenocarcinoma:implieations for a standardized scoring system[J].Cancer 2001.92:[33].
[19] Craig L.Jordan D B. The epidermal growth factor as a targer for colorectoal cancer therapy [J]. Seminoncol. 2005.32:52
[20] Zosia Chustecka. Sunitinib and Sorafenib Confirm Efficacy in Renal Cell Carcinoma [J]. N Engl J Med. 2007.356:115.
[21] Haynes PA ,Gygi SP ,Fig D , et al . Proteome analysis : biological assay or data achieve ? [J ] . Electrophoresis ,1998 ,19 (12) :1862-1871.
[22] Rappsilber J, Mann M. What does it mean to identify a protein in proteomics? Trends Biochem Sci 2002;27:74-78
[23] Chambers G,Lawrie L,Cash P,Murray GI. Proteomics: a new approach to the study of disease. J Pathol 2000;192:280-288
[24] Banks RE, Dunn MJ, Hochstrasser DF, Sanchez JC, Blackstock W, Pappin DJ, Selby PJ. Proteomics: new perspectives,
[25]王凤茹.电泳应注意的几个关键问题[J].生物技术通报2005,6,62-64
[26]熊兴东,刘新光,李恩民.双向电泳技术及其在肿瘤研究中的应用[J].MODERN ONCOLOGY,2005,113(12):270-272.
[27]朱玉光李玮.磁性高分子微球的制备及其在生物医学上的应用[J].胶体与聚合物2006,24(4)43-45.
[28]李洪利.亲和层析技术在现代蛋白质研究中的应用及新发展.海洋湖沼通报.2005,2:87-89.
[29]杨芄原,钱小红.生物质谱技术与方法[M].科学出版社1999,1-100.
[30] Howard W,John C,Pau1.Neoplasms of the stomach,Cancer Medicine,E5th[J].American Cancer Society,2001,1355.
[31] Merchant M,Weinberger SR.Recent advancements in surface-enhanced laser desorption ionization-time of flight。mass spectrometry[J].Electrophoresis,2000,21:1164 -1177.
[32] Issaq HJ,VeenstraTD,ConradsTP,et al,The SELDI TOFMS approach to proteomics:protein profiling and biomarker identification[J].Biochem Biophys Res Commun,2002,292:587-592.
[33] Vihinen M. Bioinformatics in proteomics. Biomol Eng 2001;18:241-248.
[34] Fenyo D.Identifying the proteome:software tools. Curr Opin Biotechnol 2000;11:391-395.
[35] Wojcik J, Schachter V. Proteomic databases and software on the web. Brief Bioin 2000;1:250-259
[36] Mann M, Pandey A. Use of mass spectrometry-derived data to annotate nucleotide and protein sequence databases. Trends Biochem Sci 2001;26:54-61.
[37] Shevchenko A, Sunyaev S, Loboda A, Shevchenko A, Bork P, Ens W, Standing KG. Charting the proteomes of organisms with unsequenced genomes by MALDI-quadrupole time-of-flight mass spectrometry and BLAST homology searching. Anal Chem 2001;73:1917-1926.
[38] Maggio ET,Ramnarayan K. Recent developments in computational proteomics. Trends Biotechnol 2001;19:266-272.
[39] Frankfurt, Olga ; Licht,Jonathan D ; Tallman, MartinSetal. Molecular characterization of acute myeloid leukemia and its impacton treatment[J]. Leukemia, 2007,29(6):635–649
[40] Kuendgen A,Stupp C,Aivado M,et al.Treatment of myelodys-plastic syndromeswith valproic acid alone or in combination with all-trans retinoic acid.Blood, 2004,104:1266-1269
[41] Witzig TE.Kaulmann SH.Inhibition of the phosphatidylinositol 3-kinase/ mammalian arget of rapamycin pathway in hematologic malignancies.Curr Treat Options Oncol.2006.7(4):285-294.
[42] Alaiya AA ,Franzen B ,Auer G, et al . Cancer proteomics :from identifi2 cation of novel markers to creation of artifical leaning models for tumor classification[J ] . Electrophoresis ,2000 ,21 (11) :1210-1217.
[43] Conroy SE ,Sasieni PD ,Amin V , et al . Antibodies to heat shock protein 27areassociated with improves survival inpatients with breast cancer [J ] .Br J Cancer ,1998 ,77 (19) :1875-1879.
[44] STONE RM,DEANGELO D J,KLIMEK V,et al Acute myeloid leukemiapatients with an activating mutation in FLT3 respond to a small molecule FLT3 tyrosine kinase inhibitor,PKC412[J].Blood,2005,105(1):54-60.。
[45] DeAngeloDJ,AmreinPC,KovacsovicsT,etal.Phase1/2studyof tandutinib(MLN518) plus standard induction chemotherapy innewly diagnosed acute myelogenous leukemia(AML)[abstract].Blood2006;108:617.
[46] Recher O.Beyne-RauzyO,DemurC,et al.Antileukemic activityof rapamycin in acute myeloid leukemia.Blood。2005.105(6):2527-2534.
[47] COHENL S ,ES COBARP F ,SC HARM C,etal .Three dimensional power Doppler ultrasound imporves the diagnostic accuracy for ovarian cancer prediction[ j].G ynecol Oncol,2001,82:40一48.
[48] 1 PETRICOINEF ,AR DEKANIAM ,HITTBA ,et al .Use of porteomic pattems in serum to identify ovarian cancer[ J1.L ancet, 2002 ,359:572一577.
[49] Picaluda P P,Martinei IT G,RondonunM,et al.Gemtuzumab ozogamicin for relapsed and refractory acute myeloid leukemia and myeloid sarcomas[J].Leuk Lymphoma,2004,45(9):1791-1795
[50] Sarto C,Frutiger S,Cappellano F,Sanchez JC,Doro G,Catanzaro F,Hughes GJ,Hochstrasser DF,Mocarelli P. Modified expression of plasma glutathione peroxidase and manganese superoxidise dismutase in human renal cell carcinoma. Electrophoresis 1999;20:3458-3466.
[51] Menendez V ,Fernandez2Suarez A ,Galan JA ,et al . Diagnosis of bladdercancer by analysis of urinary fibronectin [J ] . U2rology ,2005 ,65 (2) :2842289
[52] Law RH, Zhang Q, McGowan S, Buckle AM, Silverman GA, Wong W et al. An overview of the serpin superfamily. Genome Biol 2006; 7: 216.
[53] Lindblad D, Blomenkamp K, Teckman J. Alpha-1-antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model. Hepatology 2007; 46:1228–1235.
[54] Wirth PJ ,Hoang TN ,Benjamin T.Micropreparative immobilized Phgra2 dient two dimensional electrophoresis in combination with protein mi2 crosequenxcing for the analysis of human liver proeins [J]. Electro2 phoresis, 1995 ,16 (11) :1946-1960.
[55] Seow TK,Ong SE ,Liang RC , et al . Two dimensional electrophoresis map of the human hepato cellular carcinoma cell line , HCC M, and identification of the separated proteins by mass spectrometry[J ] . Elec2 trophoresis ,2000 ,21 (9) :1787-1813.
[56]俞利荣,王楠,吴高德,等.人肝癌细胞系BEL7404和正常肝细胞系L 02表达的蛋白质组双向凝胶电泳分析[J ] .科学通报,2000 ,45 (3) :170-178.
[57] Chaurand P , DaGue BB , Pearsall RS , et al. Profiling proteins from azoxymethane induced color tumors at the molecular level by matrix as 2 sisted laser desorpionP ionization mass spectrometry [ J ] . Proteomics ,2001 ,1 (10) :1320-1326.
[58] Bargagna-Mohan P, Ravindranath PP, Mohan R. Small molecule anti-angiogenic probes of the ubiquitin proteasome pathway: potential application to choroidal neovascularization. Invest Ophthalmol Vis Sci 2006; 47:4138-45.
[59] Seliger B, Fedorushchenko A, Brenner W, Ackermann A, Atkins D, Hanash S, Lichtenfels R. Ubiquitin COOH-terminal hydro-lase 1: a biomarker of renal cell carcinoma associated with en-hanced tumor cell proliferation and migration. Clin Cancer Res2007; 13:27-37.
[60] Chen YR, Juan HF, Huang HC, Huang HH, Lee YJ, Liao MY,Tseng CW, Lin LL, Chen JY, Wang MJ, Chen JH, Chen YJ.Quantitative proteomic and genomic profiling reveals metasta-sis-related protein expression patterns in gastric cancer cells. JProteome Res 2006; 5:2727-42.
[61] Okuzawa K,Franzen B ,LindholmJ , et al . Characterization of gene ex2pression in clinical lung cancer materials by two dimensional polylam2 idegel electrophoresis[J ] . Electrophoresis ,1994 ,15 (324) :382-390.
[62] Sarto C ,Marocchi A ,Sarto C , et al . Renal cell carcinoma and normal kidney protein expression[J ] . Electrophoresis ,1997 ,18 (34) :599-604.
[63] Kawauchi T, Chihama K, Nabeshima Y, Hoshino M. The in vivo roles of STEF/Tiam1, Rac1 and JNK in cortical neuronal migration. EMBO J 2003; 22: 4190-4201
[64] Lakka SS, Bhattacharya A, Mohanam S, Boyd D, Rao JS. Regulation of the uPA gene in various grades of human glioma cells. Int J Oncol 2001; 18: 71-79
[65] KeimD ,Hailat N ,Melhem R , et al . Proliferatin related expression of p19P nm23 nucleosidediphophate kinase [ J ] . J Clin Invest , 1992 , 89(6) :919-924.
[66] Ostergaard M,Rasmussen HH ,Nielsen HV , et al . Proteome profiling ofbladder squamous cell carcinomas :identification of markers that define their degree of differentiantion [J ] . Cancer Res ,1997 ,57 (20) :4111-4117.
[67] Huang J ,Hu N ,Taylor P , et al . An approach to Proteomic analysis of human tumors[J ] .Mol Carcinog ,2000 ,27 (3) :158-165.
[68] Lin JD ,Chan EC ,Weng HF , et al . Two dimensional electorophoretic analysis of membranous protein from human thyroid tissues and cancer cell lines[J ] . Electrophoresis ,1998 ,19 (18) :3213-3216.
[69] Rasmussen RK,Ji Hong ,Eddes JS , et al. Two dimensional gel database of human breast carcinoma cell expressed proteins :Anupdate[J].Elec2 trophoresis,1998 ,19 (5) :818-828.
[70] Miller A ,Mukhtar O ,Aaluri SR , et al . Two2and three2dimensional TEE differentiation of lymphoma involving the atrial septum from lipomatous hypertrophy[J]. Echocardiography ,2001 ,18 (3) :205-209.
[71]许洋.蛋白质指纹图谱技术在实验诊断与I临床医学中的研究进展.基础医学与临床.2007,27(2):334-340.
[72] Zhao L, Liu L, Wang S, et a.l Differential proteomic a-nalysis ofhuman colorectal carcinoma cell linesmetastasis-associated proteins[ J]. J Cancer Res Clin Onco,l 2007, 133(10): 771-782.
[73] RavalGN, Bharadwaj S, Levine EA, et a.l Loss of ex-pression of tropomyosin-1, a novel classⅡtumor sup-pressor that induces anoikis, in primary breast tumors[J]. Oncogene, 2003, 22(40): 6194-6203.
[74] Posadas EM, Simpkins F, Liotta LA, et a.l Proteomic a-nalysis for the early detection and rational treatment of cancer-realistic hope? [J]. Ann Onco,l 2005, 16(1):16-22.
[75] Bellacosa A. Genetic hits and mutation rate in colorectal tumorigenesis: versatility ofKnudson s theory and implica-tions for cancerprevention[J]. GenesChromosomes Canc-er, 2003, 38(4): 382-388.
[76] PolleyAC, Mulholland F, Pin C, et a.l Proteomic analy-sis reveals field-wide changes in protein expression in themorphologically normalmucosa of patients with colorectalneoplasia[J]. CancerRes, 2006, 66(13): 6553-6562.
[77] JEMAL A, MURRAY T, WARD E, et al . Cancer statistics[ J ].CA Cancer J Clin, 2005, 55 (1) : 102 30.
[78] SH I YY, WANG HC, YI N YH, et al . I dentification and analysis of tumour2 ass ociated antigens in hepat ocellular carcinoma [ J ]. B rJ Cancer, 2005, 92 (5) : 9292 934.
[79] Talieri M, Papadopoulou S, Scorilas A, et al. Cathepsin B and Cathepsin D expression in the progression of colorectal adenoma to carcinoma. Cancer Letters 2004 205 97-106.
[80] Subramanian A,Miller D M. Structural analysis of alpha-enolase.Mapp ing the functional domains involved in down-regulation of the c-myc p rotooncogene [ J ]. J Biol Chem, 2000, 275 ( 8 ) : 5958-5965.
[81] Fougerousse F, Edom-Vovard F,Merkulova T, et al. The muscle-specific enolase is an early marker of human myogenesis [ J ]. J Muscle Res CellMotil, 2001, 22 (6) : 534-544.
[82] KellerA, Rouzeau J D, Farhadian F, et al. Differential exp ression ofα- andβ-enolase genes during rat heart development and hypertrophy[ J ]. Am J Physiol, 1995, 269 (6Pt2) : H1843-H1851.
[83] Kang HJ, Jung SK, Kim SJ, et al. Structure of human alpha-enolase ( hENO1) , a multifunctional glycolytic enzyme [ J ]. Acta Crystallogr D Biol Crystallogr, 2008, 64 (6) : 651-657.
[84] [TerrierB, Degand N, Guilpain P, et al. Alpha2enolase: a target of anti-bodies in infectious and autoimmune diseases [ J ]. Autoimmun Rev,2007, 6 (3) : 176-182.
[85] KellerA, Peltzer J, Carpentier G, et al. Interactions of enolase isoforms withtubulin and microtubules duringmyogenesis [ J ]. Biochim Biophys Acta, 2007, 1770 (6) : 919-926.
[86] Perconti G, Ferro A, Amato F, et al. The Kelch protein NS1-BP interacts with alpha-enolase /MBP-1 and is involved in c-myc gene transcriptional control [ J ]. Biochim Biophys Acta, 2007, 1773 ( 12 ) :1774-1785.
[87] Sousa LP, BrasilBS, Silva BM, et al. Characterization of alpha-enolase as an interferon-alpha - alpha 1 regulated gene [ J ]. FrontBiosci, 2005,10: 2534-2547.
[88] Jorgensen L G,Osterlind K, Genolla J ,et al. Serum neuron-specific enolase (S-NSE) and the prognosis in smallcell lung cancer (SCLC) :a combined multivariable analysis on data from nine centres. Br J Cancer ,1996 ,74 :463-467.
[89] Kinloch A, TatzerV,Wait R, et al. Identification of citrullinated alpha-enolase as a candidate autoantigen in rheumatoid arthritis[ J ].Arthritis Res Ther, 2005, 7 (6) : R1421-1429.
[90] Ren G, Adamus G. Cellular targets of anti-alpha-enolase autoanti-bodies of patientswith autoimmune retinopathy[ J ]. J Autoimmun,2004, 23 (2) : 161-167.
[91] Nahm D H, Lee K H, Shim J Y. Identification of alpha-enolase as an autoantigen associated with severe asthma [ J ]. J Allergy Clin Immunol, 2006, 118 (2) : 376-381.
[92] Takashima M, Kuramitsu Y, Yokoyama Y, et al. Overexp ression of alpha enolase in hepatitis C virus-related hepatocellular carcinoma: association with tumor p rogression as determined by p roteomic analysis[ J ]. Proteomics, 2005, 5 (6) : 1686-1692.
[93] Chang G C,Liu K J, Hsieh C L, et al. Identification of alpha-enolase as an autoantigen in lung cancer: its overexp ression is associated with clinical outcomes[ J ]. Clin Cancer Res, 2006, 12 ( 19) :5746-5754.
[94] Roozendaal C, ZhaoMH, Horst G, et al. Catalase andα-enolase: two novel granulocyte autoantigens in inflammatory bowel disease ( IBD ) [ J ]. Clin Exp Immunol, 1998, 112 (1) : 10-16.
[95] Vermeulen N, Arijs I, Joossens S, et al. Anti-α-enolase antibodies in patientswith inflammatory bowel disease [ J ]. Clin Chem, 2008, 54(3) : 534-541 .
[96] Durany N, Joseph J, Campo E, et al. Phosphoglycerate mutase, 2, 3 bisphospho-glycerate Phosphatase, creation kinase and enolase activity and isoenzymes iin lung, colon and liver carcinomas [ J ]. Br J Cancer,1997, 76 (9) : 1139-1149
[97] Stieruma R, GaspariM, Dommels Y, et al. Proteome analysis reveals novel p roteins associated with p roliferation and differentiation of the colorectal cancer cell line Caco-2 [ J ]. Biochim Biophys Acta, 2003,1650 (1-2) : 73-91.
[98] KatayamaM, Nakano H, Ishiuchi A, et al. Protein pattern difference in the colon cancer Protein pattern difference in the colon cancer cell lines examined by two-dimensional differential in-gel electrophoresis and mass spectrometry [ J ]. Surg Today, 2006, 36 (12) : 1085-1093.
[99] WangLH, Fang XC, Pan GZ. Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis [ J ]. Gut, 2004, 53(8) : 1096-1101.
[100] Bassotti G, VillanacciV, Cathomas G, et al. Enteric neuropathology of the terminal ileum in patients with intractable slow-transit constipation[ J ]. Hum Pathol, 2006, 37 (10) : 1252-1258.
[101]韩金凤,王芳癌性贫血的研究进展辽宁中医药大学学报2009, 1 1 (10): 118-119
[102]沈文香,陈敏斌,沈刚,周丽娜重组人促红细胞生成素治疗肿瘤化疗中贫血的临床研究,南京医科大学学报(自然科学版)2008 ,28 (8 ):1054- 1056
[103]曹传武,徐家华,徐霁充,张家兴,王杰军回顾方法分析大肠癌的部位、分期、营养状况、治疗方法、性别、年龄等因素与贫血的相关性。同济大学学报(医学版) 2009,30(1 ):52-55
[104]房朝辉,李魁秀,宋藏珠,牛书怀,王争国探讨Ⅱ、Ⅲ期宫颈癌患者血红蛋白水平与放射治疗近期、远期疗效的关系河北医科大学学报2004 ,25 (4 ):200-201
[105]秦瑞,吴达荣,胡俊,毕向军研究对晚期癌性贫血患者血清促红细胞生成素( EPO)的水平及其对患者贫血症状作用的临床意义。临床和实验医学杂志2006,5(2)107-108
[106] Kuroda N ,Narase , Miyazaki E , et al . Vinculin : its possible use asmarker ofnormal collecting ducts and renal neoplasms with collecting duct system phenotype[J ] .Mod Pathol ,2000 ,13 (10) :1109 - 1114.
[107] MacDonald N, Shivers W, Narum D,et al. Endostatin binds tropomyosin. A potential modulator of the antitumor activity of endostatin [J]. J Biol Chem,2001,276(27):25190-25196.
[108] Sibley K, Cuthbert-Heavens D, Knowles MA. Loss of heterozy- gosityat4p16.3and mutation of FGFR3in transitional cell car-cinoma [J]. Oncogene,2001,20:686-691.
[109] Vokes EE, Crawford J, Bogart J, et al . Concurrent chemoradi o2 therapy for unresectable stageⅢnon2small cell lung cancer[ J ].Clin Cancer Res, 2005, 11 (2) : 5045 - 5050.
[110] Bois PR, OπHara BP, Nietlis pach D, et al . The vinculin bindingsites of talin and alpha2 actinin are sufficient t o activate vinculin [ J ]. J Biol Chem, 2006, 281 (11) : 7228 - 7236.
[111] I zard T, Evans G, Borgon RA, et al . Vinculin activation by talinthr ough helical bundle conversion [ J ]. Nature, 2004, 427(6970) : 171 - 175.
[112] Kelly DF, Taylor DW, Bakolitsa C, et al . Structure of the alpha2 actinin2 vinculin head domain comp lex determined by cryo2 elec2tron micr oscopy[ J ]. J Mol Biol, 2006, 357 (2) : 562 - 573.
[113] Roberts GC, Critchley DR. Structural and bi ophysical p roperties of the integrin2 ass ociated cyt oskeletal p r otein talin [ J ]. Biophys Rev, 2009, 1 (2) : 61 - 69.
[114] Xing B, Thuppals, Jedsadayanmata A, et al . TA205, an anti2talin monocl onal antibody, inhibits integrin2talin interacti on [ J ]. FEBSLett, 2006, 580 (8) : 2027 - 2032.
[115] Monkley SJ, Zhou XH, Kinst on SJ, et al . Disrup ti on of the talin gene arrestsmouse development at the gastrulati on stage[ J ]. DevDyn, 2000, 219 (4) : 560 - 574.
[116] RobertsGC, Critchley DR. Structural and biophysical properties of the integrin-associated cytoskeletal protein talin[ J]. Biophys Rev, 2009, 1(2): 61-69.
[117] ]Xing B, Thuppals, Jedsadayanmata A, et a.l TA205, an anti-talin monoclonal antibody, inhibits integrin-talin interaction[J]. FEBS Lett, 2006, 580(8):2027-2032.
[118] Monkley SJ, Zhou XH,Kinston SJ, et a.l Disruption of the talin gene arrestsmouse developmentat the gastrulation stage[J]. DevDyn, 2000, 219(4): 560-574.
[119]杨红军,丁彦青,周军.大肠癌组织中talin mRNA的表达及意义[J].山东医药, 2008, 48(3): 1-2.
[120] Humphries JD, Wang P, Streuli C, et a.l Vinculin controls focal adhesion formation by direct interactionswith talin and actin[J]. JCellBio,l 2007, 179(5): 1043-1057.
[121] Vokes EE, Crawford J, Bogart J, et a.l Concurrent chemoradio-therapy for unresectable stageⅢnon-small cell lung cancer[J].Clin CancerRes, 2005, 11(2): 5045-5050.
[122] BoisPR, O Hara BP, Nietlispach D, et a.l The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin [J]. J BiolChem, 2006, 281(11): 7228-7236.
[123] Izard T, EvansG, Borgon RA, et a.l Vinculin activation by talin through helical bundle conversion [ J]. Nature, 2004, 427(6970): 171-175.
[124] Kelly DF, TaylorDW, Bakolitsa C, et a.l Structure of the alpha-actinin-vinculin head domain complex determined by cryo-elec- tronmicroscopy[J]. JMolBio,l 2006, 357(2): 562-573.
[125] Garcia-Alvarez B, de Pereda JM,Calderwood DA, et a.l Struc-tural determinants of integrin recognition by talin[J].MolCel,l2003, 11(1): 49~58.
[126] LingK,Doughman RL,FirestoneAJ, et a.l Type I gamma phos-phatidylinositol phosphate kinase targets and regulates focal ad-hesions[J].Nature, 2002, 420(6911): 89~93.
[127] DiPaoloG,PellegriniL,Letinic K, et a.l Recruitment and regu-lation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin[J].Nature,2002,420(6911):85~9.
[128] LingK,Doughman RL, IyerVV, et a.l Tyrosine phosphorylation of type Igamma phosphatidylinositol phosphate kinase by Srcregulates an integrin-talin switch[ J]. J Cell Bio,l 2003, 163(6): 1339~49.
[129] Tadokork S, ShattilSJ,EtoK, eta.l Talin binding to integrin be-ta tails: a final common step in integrin activation[J]. Science,2003, 302(5642): 103~6.
[130] Barsukov IL, PrescotA,BateN, eta.l Phosphatidylinositolphos-phate kinase typel gamma and betal- integrin cytoplasmic do-main bind to the same region in the talin FERM domain[ J]. JBiolChem, 2003, 278(33): 31202~9.
[131] Hynes RO. Integrins: bidirectiona,l allosteric signalingmachines [J].Cel,l 2002, 110(6): 673~87.
[132] Woodside DG, Liu S, Ginsberg MH. Integrin activation [ J]·ThrombHaemost, 2001, 86(1): 316~23.
[133] Hughes PE,Diaz-GonzalezF,LeongL, eta.l Breaking the in-tegrin hinge. A defined structural constraint regulates integrinsignaling[J]. J BiolChem, 1996, 271(12): 6571~4.
[134]刘勇,顾康生Talin、vinculin在食管癌中的表达及其临床意义临床肿瘤学杂志2009,14(9):787-790
[135] RobertsGC, Critchley DR. Structural and biophysical properties of the integrin-associated cytoskeletal protein talin[ J]. Biophys Rev, 2009, 1(2): 61-69.
[136] Xing B, Thuppals, Jedsadayanmata A, et a.l TA205, an anti-talin monoclonal antibody, inhibits integrin-talin interaction[J]. FEBS Lett, 2006, 580(8): 2027-203
[137] Humphries JD, Wang P, Streuli C, et a.l Vinculin controls focal adhesion formation by direct interactionswith talin and actin[J]. JCellBio,l 2007, 179(5): 1043-1057.
[138] Vokes EE, Crawford J, Bogart J, et a.l Concurrent chemoradio-therapy for unresectable stageⅢnon-small cell lung cancer[J]. Clin CancerRes, 2005, 11(2): 5045-5050.
[139] BoisPR, O Hara BP, Nietlispach D, et a.l The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin [J]. J BiolChem, 2006, 281(11): 7228-7236.
[140] Xing B, Thuppal S, Jedsadayanmata A, et al. TA205, an anti -talin monoclonal antibody, inhibits integrin - talin interaction [J]. FEBS Lett, 2006, 580(8):2027~ 2032
[141] Kelly DF, TaylorDW, Bakolitsa C, et a.l Structure of the alpha-actinin-vinculin head domain complex determined by cryo-elec- tronmicroscopy[J]. JMolBio,l 2006, 357(2): 562-573.
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